The long way to diagnosis: Attention Disorder, Alcohol Addiction or Congenital Disorder of Glycosylation?-A case report

The long way to diagnosis: Attention Disorder, Alcohol Addiction or Congenital Disorder of Glycosylation?-A case report | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Case Report The long way to diagnosis: Attention Disorder, Alcohol Addiction or Congenital Disorder of Glycosylation?-A case report Timo Jendrik Faustmann, Lukas Hensel, Armin Bahic, Yoshinao Wada, and 4 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5679698/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 29 Apr, 2025 Read the published version in BMC Psychiatry → Version 1 posted 6 You are reading this latest preprint version Abstract Attention deficit hyperactivity disorder (ADHD) is a relatively common disorder in clinical psychiatry. Patients often suffer from symptoms long before the diagnosis due to an overlap with other psychiatric differential diagnosis. Importantly, alcohol addiction and other illicit drug dependence and withdrawal symptoms mimicking ADHD symptoms should be ruled out. Here we present a rare case of a young female patient with symptoms of ADHD and an extremely high carbohydrate-deficient transferrin (CDT) of 19,6% (< 1,3%) indicating the presence of a congenital disorder of glycosylation (CDG). A thorough diagnostic workup excluded alcohol addiction as a cause of the constantly high CDT levels. The CDT test was positive due a transferrin mutation affecting the glycosylation site. Nevertheless, psychiatric symptoms can be due to metabolic disorders which should be considered. Further, substance-use disorders (SUD) are a critical and potentially complicated differential diagnosis concerning diagnostic procedures and treatment in ADHD. ADHD CDT CDG case report psychostimulants Figures Figure 1 Background ADHD Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder that begins in childhood and persists into adulthood in up to 15–60% of patients. Depending on the age, approximately 2–5% of the population is affected by ADHD [ 1 – 3 ]. Core symptoms include inattentiveness, impulsivity and hyperactivity. Progressing from childhood to adulthood, hyperactivity usually turns into an inner restlessness in adults [ 4 ]. Moreover, patients may present with comorbidities like SUD which are very comment in ADHD and further are potentially misdiagnosed with other conditions e.g. mood disorders or personality disorders [ 2 ] [ 5 , 6 ]. According to German guidelines the diagnosis of ADHD can be made after evaluation of the clinical presentation and standardized psychometric testing [ 7 ]. Standardized instrumental diagnostics is not recommended, but commonly routine blood parameters, urine toxicology screening, brain magnetic resonance imaging (MRI) and carbohydrate-deficient transferrin are used to evaluate the somatic differential diagnosis and potential substance abuse and should be taken into account before starting a medication [ 7 ]. Further in case of consumption (e.g. alcohol) abstinence during the diagnostic process is important but often not possible [ 8 ] [ 9 ]. Treatment of ADHD is multimodal including psychostimulants with significant effects on symptom control, psychoeducation, psychotherapy and neurofeedback training [ 7 ]. CDT Transferrin is an iron-binding glycoprotein transporting iron throughout the human body. Carbohydrate-deficient transferrin (CDT) is mainly known as a long-term marker for alcohol abuse and describes transferrin isoforms which are deficient in their structure and appear after ethanol consumption of about 50-80g/d for more than 10–15 days. As studied in 2500 individuals, the sensitivity for alcohol consumption was 82% and the specificity was 97%, respectively. The reason for the hypoglycosylation is not clear but could be an acetaldehyde-mediated inhibition of glycosyl transfer [ 10 ] [ 11 ] [ 12 ]. CDT is important for assessing possible alcohol dependence and differentiating alcohol abuse from enzyme-inducing medication [ 13 ]. Variations of CDT levels have been associated with pregnancy [ 14 ], fructose intolerance and galactosemia [ 15 ] and chronic obstructive pulmonary disease (COPD) [ 16 ]. Further reasons for an increase in CDT could be genetic variants of transferrin, chronic active hepatitis, primary biliary cirrhosis and congenital disorders of glycosylation (CDG) [ 10 ]. CDG CDG are a heterogeneous group of genetic disorders that include various defects in the processing or synthesis of glycoproteins [ 17 ]. Around 160 genetic conditions have been described commonly leading to dysfunctional hypo- or dysglycosylation of lipids and proteins [ 18 ] [ 19 ]. Symptoms range from mild to severe including the failure to thrive, intellectual disability, developmental delay, facial dysmorphism, muscular hypotonia, ataxia due to cerebellar atrophy, epilepsy, liver disease, endocrinopathies, retinopathy, coagulopathy and hypoglycemia [ 20 , 21 ] Prevalence in Europe is around 0.1–0.5/100000 but appears to be underdiagnosed [ 22 ]. The diagnostic workup consists of a CDT screening, transferrin isoform analysis with high-performance liquid chromatography (HPLC), protein-linked glycan analysis with mass spectroscopy and genomic sequencing. Yet, biochemical pathogenesis is diverse [ 20 , 23 ] and to date, mainly four groups are distinguished: disorders of N- linked glycosylation, disorders of O-linked glycosylation, combined N- and O-linked/multiple disorders of glycosylation and lipid and glycosylphosphatidylinositol anchor biosynthesis defects [ 24 ]. CDG type I affecting the glycan synthesis and CDG type II affecting glycan processing are the subdivisions of disorders of N-glycosylation [ 25 ]. The treatment depends on the exact form of CDG. Basically, three basic treatment concepts have been suggested: substrate (precursor) supplementation, cofactor supplementation and pharmacological chaperons. Further, non-causative and other treatments have been discussed [ 24 ]. For example, oral mannose can be used for mannose-6 phosphate isomerase- (MPI-) CDG, galactose for phosphoglucomutase-1- (PGM1-) CDG to increase coagulation factors and decrease serum transaminase levels, liver transplantation in MPI-CDG and coiled-coil domain containing 115- (CCDC115-) CDG, bone marrow transplantation in phosphoglucomutase-3- (PGM3-) CDG and in further variants treatment of specific symptoms like pericarditis, hypothyroidism and hypoglycemia[ 20 ] [ 22 ]. The here presented case points towards interesting overlaps of ADHD symptoms, SUD and metabolic diseases. Case Presentation Instrumental diagnostics: Written informed consent was obtained from the patient for the publication of this case report. The CARE guidelines for case reports were followed [ 26 ]. Routine blood parameters including CDT were performed. Additionally, urine toxicology screens including ethyl glucuronide were conducted. Genetic screening for a mutation of Aldolase B gene and Transferrin gene was performed. Breath alcohol and Clinical Institute Withdrawal Assessment for Alcohol-Revised (CIWA-Ar) score was used to rule out signs of alcohol intoxication and withdrawal [ 27 ]. Transferrin isoforms were analyzed using HPLC. Liver MRI, electrocardiogram, internal medicine consultation, abdominal ultrasound and neurological examination were additionally performed. Psychometrics: For ADHD testing we used the world health organization (WHO) Adult ADHD Self-Reported Scale (ASRS-V1.1). The self-report screening questionnaire consists of 6 questions (minimum 4 questions with significant intensity required) asking for the severity of inattention, hyperactivity, and impulsivity symptoms listed in Diagnostic and Statistical Manual of Mental Disorders 4th edition (DSM-IV) [ 28 ] and ADHS-SB/HASE-SB (ADHS- Selbstbeurteilungsbogen/Homburger ADHS-Skalen für Erwachsene Selbstbeurteilungsbogen) self- disclosure questionnaire consisting of 18 questions (Cut-Off for significant ADHD symptoms = 18 points) [ 29 ] [ 30 ] followed by a standardized interview in German language - the integrated diagnosis of ADHD in adults revised version (IDA-R) - including a semi-structured interview (9 questions on attention-deficits and 9 questions on hyperactivity, minimum 5 questions with severe symptoms required for attention-deficits and minimum 5 questions with severe symptoms required for hyperactivity) to evaluate if symptoms meet the criteria according to DSM-5 [ 31 ]. Wender-Utah rating scale (German short version, WURS-K, 25 questions, Cut-Off for significant ADHD symptoms during childhood ≥ 30 points) was used to evaluate childhood symptoms of ADHD [ 32 ] [ 33 ]. Further, written teacher school reports from elementary school (grades 1–4) were screened giving an impression of how the patient behaved in elementary school. Multiple Choice Word Test-B (MWT-B) consists of 37 questions and was used for the intelligence diagnostic (age validated intelligence quotient) [ 34 ]. Becks Depression Inventory II self-report questionnaire (BDI-II) comprising 21 questions was used to evaluate symptoms of depression (0–8 points = no depressive symptoms, 9–13 points = minimal depressive symptoms, 14–19 points = mild depressive symptoms, 20–28 points = medium depressive symptoms, > 28 points = severe depressive symptoms) [ 35 ] [ 36 ]. D2 concentration-endurance test (D2 test, validated by age, concentration can be above average, average or below average) [ 37 ] was used to evaluate the concentration. The German version of PSDI (Personality Styles and Disorder Inventory) consists of 140 items evaluating the non- pathological equivalents of 14 personality disorders in DSM IV and International Statistical Classification of Diseases, 10th revision, German Modification, Version 2024 (ICD-10-GM Version 2024) and was used to evaluate signs of personality accentuation (validated by age, t-values between 40–60 are average) [ 38 ]. Autism Quotient (AQ) consists of 50 items [ 39 ] and was used to differentiate ADHD symptoms from possible symptoms of an autism spectrum disorder (Cut-Off for significant symptoms ≥ 32 points). Global assessment of function (GAF) was used to evaluate the general level of psychosocial functioning (Score ranges from 1 (severe impairment in psychosocial functioning) to 100 (high psychosocial functioning)) [ 40 ]. Case A 30-year-old Turkish descendent, medical assistant, female patient was transferred by a psychiatrist to our specialized outpatient clinic in 2023 with symptoms of ADHD (difficulties in reading and writing, focusing, concentration, feelings of stress and permanent assessment) for completion of an ADHD diagnostic. She received no medication when she arrived at our department for the first time. The patient reported no other somatic diseases. There was no family history of severe physical or mental illnesses. The patient reported a history of depression and suspicion of ADHD, but without having received a work-up for ADHD. The patient had been on a previous medication of sertraline, escitalopram, aripiprazole, olanzapine and diazepam, but without a psychiatric inpatient treatment. Before she was put on sick leave by her general practitioner because of a somatic symptom disorder in 2021 and 2022 (Fig. 1 ). At the time of consultation at our clinic a somatic symptom disorder could not be diagnosed. She reported symptoms of attention deficit and difficulties in focusing since her youth. School reports from elementary school (grades 1–4) revealed strong symptoms of ADHD including inattention, easy distraction by other pupils, concentration difficulties, aids and additional time for tasks, problems implementing complex tasks, not targeted, inaccuracy, difficulties in writing with outlet errors. She failed her final examination in high school and had to repeat the 11th grade. During the time of consultation in our clinic the patient continued working as a medical assistant. During the diagnostic process in our outpatient clinic, she revealed the following scores in table 1: Mental status exam revealed a patient oriented to person, place and time with cooperative behavior. The motor activity revealed some psychomotor agitation and some fidgeting with her hands. The attention span was reduced and the concentration was mildly impaired. The thought form was diffuse. The affect was appropriate. The mood was euthymic. The thought content was normal. The patient denied suicidal or homicidal ideations. Neurological examination was unremarkable. In total the diagnosis of ADHD combined type was made according to the German guidelines for ADHD, the European consensus statement and ICD-10-GM Version 2024 without comorbidities like depression, autism, personality disorders, psychotic disorders or somatic symptom disorders according to ICD-10 [ 7 ] [ 41 ] [ 42 ]. In parallel before starting ADHD-medication routine blood parameters including blood cell count, coagulation, liver enzymes, kidney parameters, electrolytes and thyroid parameters were normal. Monocytes were slightly increased to 10.8% on the 22nd of June 2023, 11.4% on the 28th of July and 10.8% (2.0-9.5) on the 10th of August 2023. Lactate dehydrogenase (LDH) was 288 U/l (< 250) on the 28th of July 2023. Immunofixation was negative. Anti-nuclear antibodies (ANA), anti-mitochondrial antibodies (AMA), anti-soluble liver antigen antibodies (SLA), liver kidney microsome antibodies (LKM), anti-smooth muscle antibodies (ASMA), cytoplasmic anti-neutrophil cytoplasmic antibodies (c-ANCA), perinuclear ANCA (p-ANCA) were all negative. Atypical ANCA (X-ANCA) were 1:32 (1:<10). Serum protein electrophoresis was negative. Beta 1 globulin was 4,6% (4,9 − 7,2). Transferrin was 1,65 g/l (1.80–3.82) and ferritin was 47,7% (16–45%) on the 28th of July 2023. An unusually high CDT of 19.6% (< 1,3%) was found on the 23rd of June 2023 followed by 19,1% on the 27th of June 2023 and 23,2% on the 10th of August 2023. Yet, urine ethyl glucuronide was negative (< 0,5 mg/l) on the 14th of July 2023 and 10th of August 2023, repeatedly indicated absence of alcohol intake. Urine toxicology screening was also negative for opioids, cannabinoids, amphetamines and cocaine on the 27th of June 2023, 28th of July 2023 and 10th of August 2023. Breath alcohol and CIWA-Ar score was negative on the 27th of July and 28th of July. The anamnesis by the husband also was not suggestive of addiction. In conclusion, after repeated consultations with the patient and her husband and consistent laboratory results, alcohol addiction was ruled out. Pregnancy test was negative on the 27th of June 2023. In parallel, because of the high CDT transferrin isoforms were analyzed using HPLC and revealed high Disialo-Transferrin of (22,8% ( 85%)). Other parameters revealed 0.0% of Monosialo-Transferrin (0.0%), 2,4% of Trisialo-Transferrin (< 6.5%), and 4,8% of Pentasialo-Transferrin (< 15%) respectively, pointing towards evidence for a congenital disorder of glycosylation. Additionally, genetic testing ruled out hereditary fructose intolerance, a known cause of transferrin hypoglycosylation. Native liver MRI-scan was normal; the patient rejected receiving contrast agent. Abdominal ultrasound and internal medicine consultation were negative for any abdominal and internal medicine abnormalities. Electrocardiogram was normal. An additional MRI scan of the brain was rejected by the patient. After extensive diagnostic procedures in August 2023, partially retarded methylphenidate was started with 5mg/day and increased up to 10 mg/day and later 15 mg/day. This was not well tolerated, and the patient reported headache, agitation and nausea so that the medication was changed to lisdexamfetamine in a dosis of 30 mg/day due to mentioned side effects. The dosis was increased to 50 and later on to 70 mg/day by the beginning of 2024. Symptoms decreased and the patient felt better during the day. Drug levels revealed 104 ng/ml amphetamines (20–100 ng/ml) in the blood on the 29th of May 2024 and symptom scores in the ADHS-SB decreased (from 43 in 2023 to 34 in May 2024 and 18 in August 2024). Further, GAF improved from 40 in 2023 (Burdened by psychosocial stress related to work) to 65 in 2024 (Improvement at work, finished exam at work) (table 1). Since the patient improved with lisdexamfetamine but still reported symptoms a further diagnostic and therapy regarding CDG was recommended but rejected by the patient. The patient wanted to postpone the decision of further diagnostic into the future if symptoms remain. In May 2024 transferrin analysis revealed the heterozygous transferrin mutation c.1295A > G that destroys the glycosylation site at the asparagine 432. The amino acid changes due to the mutation as well as the lack of glycan at this site were confirmed by mass spectrometry. Thus, transferrin in the patient has only one glycosylation site left and the hypoglycosylation is not indicative of CDG disease. Discussion In this case we report a young female patient who initially presented with symptoms of ADHD. The case is unique because of the following reasons: The abnormally high serum CDT was initially considered as a likely indicator for an overlap with a possible alcohol dependence. Stigmatization of psychiatric patients due to false positive biomarkers. These findings led to a delayed start of the ADHD therapy because of the more complex differential diagnosis for rare causes of elevated CDT. Diagnostic/Treatment of ADHD and co-morbid substance abuse. Co-existing ADHD together with CDG (which was suspected in first place) and possible role of glycosylation related to ADHD. Lisdexamfetamine was a good treatment option in this case of ADHD. Complex possible metabolic and genetic findings in psychiatric disorders. Reason 1–4: Problems of co-existing ADHD and SUD: The complex situation of ADHD and SUD includes the problems of an adequate diagnostic under possible substance abuse. It can be discussed that during the diagnostic procedure in cases of addiction a first screening for ADHD symptoms can be done but complete testing should be performed after withdrawal cause intoxication and withdrawal symptoms can mimic ADHD symptoms [ 8 ] [ 9 ]. Further, the treatment with a substance like methylphenidate and lisdexamfetamine (psychostimulants) potentially is discussed to be misused in e.g. 5–35% of cases in high school students and college students and abuse and diversion potential can be discussed. Further, additionally effects on the cardiovascular system like mild increase in blood pressure and heart rate need to be discussed and are important if further psychiatric and somatic comorbidities exist [ 43 ] [ 44 ] [ 45 ] [ 46 ]. These facts have to be taken into account if in parallel a continued intake of another substance due to an abuse exist which further might complicate the therapy [ 9 ]. In conclusion, a close screening and monitoring of ADHD medication use is recommended [ 44 ]. Around 50% of patients with ADHD have SUD and the role of “self-medicated” ADHD symptoms can be discussed. The SUD therapy can suffer under a not treated ADHD and ongoing substance abuse can limit the ADHD therapy. The use of non-stimulant pharmacotherapy needs to be discussed for cases of ADHD and SUD [ 9 ] [ 47 ]. Interestingly, psychostimulants are discussed to reduce risky behavior like substance abuse among patients with ADHD and prevent the development of SUD, but physicians often are not sure about the exact treatment of patients presenting with ADHD and substance abuse at the same time [ 48 ]. In a meta- analysis comparing follow up studies the use of psychostimulants in childhood was related to a reduction in the risk for drug and alcohol addiction later in life [ 49 ]. Further, different administration (e.g. oral, intravenous) revealed that orally intake of methylphenidate constrains abuse [ 50 ]. Further, the occurrence of e.g. possible lisdexamfetamine abuse has been discussed but the concerns could not be substantiated in patients [ 51 ]. Reason 5: Co-existing ADHD together with CDG (which was suspected in first place) and possible role of glycosylation related to ADHD : To date, only few cases have linked abnormal glycosylation to attention disorders including ADHD. For example, alpha-1,3-glucosyltransferase- (ALG8-) CDG has been found to show intellectual disabilities besides other organ manifestations including musculoskeletal, dermatologic and cardiac symptoms [ 52 ]. Further, alterations of glycan composition of glycoproteins were found in patients with ADHD and it was discussed that these alterations are connected to further findings of patients with the diagnosis of CDG and changes in behavior and neurological activity and variants in fucosyltransferase 8 (FUT8) at the same time [ 53 ] [ 54 ]. Another case with Conserved Oligomeric Golgi (COG-)CDG was reported to include symptoms of ADHD in the clinical presentation [ 55 ]. Taken together the exact pathomechanism of symptoms of ADHD occurring together with a possible CDG is not clear. However, the association may be overlooked if standard serum markers such as liver enzymes show normal serum levels or in patients with overlapping substance abuse. Previously, neurodevelopmental disorders such as autism have been described in CDG. Further N-glycosylation abnormalities were described in ADHD [ 56 , 57 ]. Concerning the here described symptoms of ADHD together with a suspected occurrence of CDG at the same time one mechanism of pathology can be a missing N-linked glycosylation which is important for the membrane localization of the dopamine D5 receptor [ 58 ]. This receptor was discussed to be important in ADHD [ 59 ]. Further, contradicting glycosylation of the dopamine transporter (DAT) is more efficiently in transporting dopamine and was discussed to be involved in the vulnerability of midbrain dopamine cells in Parkinson’s disease [ 60 ]. Since dopamine and DAT are one therapeutical target in ADHD treatment this could be one possible mechanism when considering ADHD and CDG at the same time. Reason 6: Lisdexamfetamine was a good treatment option in this case of ADHD: In the present case, treatment with methylphenidate was not well tolerated. Lisdexamfetamine was a good alternative option and the patient reported symptom relief with 30 mg and later 70 mg. Lisdexamfetamine is a long-acting amfetamine prodrug and approved by the FDA (US Food and Drug Administration) and EMA (European Medicine Agency) for ADHD in adults inhibiting the dopamine and noradrenaline transporters, inhibiting the transmitter reuptake and increasing the dopamine and noradrenaline release by being taken up into neuronal cells and acting on the vesicular monoamine transporters [ 61 ] [ 62 ] [ 51 ]. Comparable cases using lisdexamfetamine have not been reported before. Reason 7: Complex possible metabolic and genetic findings in psychiatric disorders: In the end the diagnosis of a CDG was not likely due to the finding of a transferrin mutation which was previously described in a healthy patient [ 63 ]. Polymorphisms in the transferrin gene have been found in patients with schizophrenia and were discussed to affect oligodendrocytes and myelin formation but the role in ADHD remains unclear [ 64 ]. Even if no clear evidence for a metabolic disorder was found it can be discussed as a reason for the development of psychiatric symptoms like in ADHD [ 65 ] [ 66 ]. Lastly, it is not clear what effect the found transferrin mutation might have concerning psychiatric symptoms and what other findings could have been made concerning metabolic diseases. The found mutation can be discussed as an incidental finding. Conclusion This work refers to a case report but points towards problems of ADHD treatment in an outpatient clinic and overlaps with a possible SUD. A delayed start of medication was found in this case due to abnormal high biomarkers (CDT). Firstly, the patient rejected further diagnostic or treatment for the here found glycosylation abnormalities (possible CDG) and was satisfied with lisdexamfetamine due to an improvement with the therapy, but it needs to be discussed that in cases of metabolic disorders psychiatric symptoms can occur. Secondly, the later found transferrin mutation points towards a genetic case and the effects on psychiatric symptoms due to these findings are not clear. Further, we consider CDT as an important diagnostic tool in patients with ADHD because (beside relevance in alcohol consumption) overlaps with glycosylation abnormalities are possible. Lastly, the patient rejected to do a brain MRI scan, but the diagnosis of ADHD could be made based on extensive laboratory diagnostics and the lack of a clear recommendation for a brain MRI scan in the ADHD guidelines. Limitations Due to a case report, there is a lack of generalizability. A confounding factor is the here described transferrin mutation which could be further discussed as a stigmatization for the patient regarding consumption of alcohol (high CDT). Missing further metabolic and genetic tests could have been useful to evaluate if the mentioned transferrin mutation is really affecting central nervous structures leading to symptoms of ADHD. Abbreviations ADHD: attention deficit hyperactivity disorder ADHS: Aufmerksamkeitsdefizit-/Hyperaktivitätsstörung ADHS-SB: ADHS-Selbstbeurteilungsbogen ALG8: alpha-1,3-glucosyltransferase AMA: anti-mitochondrial antibodies ANA: Anti-nuclear antibodies AQ: Autism Quotient ASMA: anti-smooth muscle antibodies ASRS-V1.1: Adult ADHD Self-Reported Scale BDI-II: Becks Depression Inventory II c-ANCA: cytoplasmic anti-neutrophil cytoplasmic antibodies CCDC115: coiled-coil domain containing 115 CDG: congenital disorder of glycosylation CDT: carbohydrate-deficient transferrin CIWA-Ar: Clinical Institute Withdrawal Assessment for Alcohol-Revised COG: Conserved Oligomeric Golgi COPD: chronic obstructive pulmonary disease DAT: dopamine transporter DSM-IV: Diagnostic and Statistical Manual of Mental Disorders 4 th edition D2 test: D2 concentration-endurance test EMA: European Medicine Agency FDA: US Food and Drug Administration FUT8: fucosyltransferase 8 HASE-SB: Homburger ADHS-Skalen für Erwachsene Selbstbeurteilungsbogen HPLC: high-performance liquid chromatography ICD-10-GM Version 2024: International Statistical Classification of Diseases, 10 th revision, German Modification, Version 2024 IDA-R: integrated diagnosis of ADHD in adults revised version LDH: lactate dehydrogenase LKM: liver kidney microsome antibodies MPI: mannose-6 phosphate isomerase MRI: magnetic resonance imaging MWT-B: Multiple Choice Word Test-B p-ANCA: perinuclear anti-neutrophil cytoplasmic antibodies PGM1: phosphoglucomutase-1 PGM3: phosphoglucomutase-3 PSDI: Personality Styles and Disorder Inventory SLA: anti-soluble liver antigen antibodies SUD: substance-use disorders WHO: world health organization WURS-K: Wender-Utah rating scale german short version X-ANCA: atypical anti-neutrophil cytoplasmic antibodies Declarations Ethics Approval Ethical approval was not required for case reports. Consent to participate Not applicable. Consent for publication Written informed consent was obtained from the patient for the publication of this case report. Competing interests The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. Funding Does not apply. Availability of data and materials Data is provided within the manuscript or supplementary information files. Acknowledgments Not applicable Author Contributions TJF: Writing – original draft, Conceptualization, Data Curation, Project administration, Figure preparation. LH: Writing – review & editing, Data Curation. AB: Writing – review & editing. YW: Writing – review & editing. MG: Data Curation. TM: Writing – review & editing, Data Curation. DK: Writing – review & editing, LS: Writing – review & editing. References Simon, V., et al., Prevalence and correlates of adult attention-deficit hyperactivity disorder: meta-analysis. 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J Clin Epidemiol, 2017. 89 : p. 218-235.DOI: 10.1016/j.jclinepi.2017.04.026. Sullivan, J.T., et al., Assessment of alcohol withdrawal: the revised clinical institute withdrawal assessment for alcohol scale (CIWA-Ar). Br J Addict, 1989. 84 (11): p. 1353-7.DOI: 10.1111/j.1360-0443.1989.tb00737.x. Kessler, R.C., et al., The World Health Organization Adult ADHD Self-Report Scale (ASRS): a short screening scale for use in the general population. Psychol Med, 2005. 35 (2): p. 245-56.DOI: 10.1017/s0033291704002892. Retz-Junginger, P., et al., [ADHD: Burden of Disease According to Subtypes in Adult Patients]. Psychiatr Prax, 2016. 43 (5): p. 279-82.DOI: 10.1055/s-0035-1552699. Rösler, M., Retz-Junginger, P., Retz, W., Stieglitz, R.-D., Homburger ADHS-Skalen für Erwachsene, 2., überarbeitete und ergänzte Auflage. CJ Hogrefe, 2021. Retz, W., et al., [Standardised psychopathological rating scales for the diagnosis of ADHD in adults]. Fortschr Neurol Psychiatr, 2013. 81 (7): p. 381-9.DOI: 10.1055/s- 0033-1335740. Retz-Junginger, P., et al., [Reliability and validity of the Wender-Utah-Rating-Scale short form. Retrospective assessment of symptoms for attention deficit/hyperactivity disorder]. Nervenarzt, 2003. 74 (11): p. 987-93.DOI: 10.1007/s00115-002-1447-4. Ward, M.F., P.H. Wender, and F.W. Reimherr, The Wender Utah Rating Scale: an aid in the retrospective diagnosis of childhood attention deficit hyperactivity disorder. Am J Psychiatry, 1993. 150 (6): p. 885-90.DOI: 10.1176/ajp.150.6.885. Lehrl, S., G. Triebig, and B. Fischer, Multiple choice vocabulary test MWT as a valid and short test to estimate premorbid intelligence. Acta Neurol Scand, 1995. 91 (5): p. 335-45.DOI: 10.1111/j.1600-0404.1995.tb07018.x. Beck, A. T., Steer, R. A., Brown, G. K., Manual for the Beck Depression Inventory - Second Edition. 1996 (San Antonio, TX: Psychological Corporation). Beck, A.T., et al., An inventory for measuring depression. Arch Gen Psychiatry, 1961. 4 : p. 561-71.DOI: 10.1001/archpsyc.1961.01710120031004. Brickenkamp, R., Zillmer, E., Test d2: Concentration-Endurance Test. CJ Hogrefe, 1998. Kuhl, J., Kazén, M., Persönlichkeits-Stil- und Störungs-Inventar (PSSI). Manual [Personality Style and Disorder inventory (PSDI). CJ Hogrefe, 2009. Baron-Cohen, S., et al., The autism-spectrum quotient (AQ): evidence from Asperger syndrome/high-functioning autism, males and females, scientists and mathematicians. J Autism Dev Disord, 2001. 31 (1): p. 5-17.DOI: 10.1023/a:1005653411471. Aas, I.H., Global Assessment of Functioning (GAF): properties and frontier of current knowledge. Ann Gen Psychiatry, 2010. 9 : p. 20.DOI: 10.1186/1744-859X-9-20. Kooij, S.J., et al., European consensus statement on diagnosis and treatment of adult ADHD: The European Network Adult ADHD. BMC Psychiatry, 2010. 10 : p. 67.DOI: 10.1186/1471-244X-10-67. ICD-10-GM Internationale statistische Klassifikation der Krankheiten und verwandter Gesundheitsprobleme, German Modification . 2024; Available from: https://www.bfarm.de/DE/Kodiersysteme/Klassifikationen/ICD/ICD-10-GM/_node.html. Harstad, E., S. Levy, and A. Committee on Substance, Attention-deficit/hyperactivity disorder and substance abuse. Pediatrics, 2014. 134 (1): p. e293-301.DOI: 10.1542/peds.2014-0992. Clemow, D.B. and D.J. Walker, The potential for misuse and abuse of medications in ADHD: a review. Postgrad Med, 2014. 126 (5): p. 64-81.DOI: 10.3810/pgm.2014.09.2801. Forns, J., et al., Risk of Major Cardiovascular and Cerebrovascular Events in Users of Lisdexamfetamine and Other Medications for Attention-Deficit/Hyperactivity Disorder in Denmark and Sweden: A Population-Based Cohort Study. Neurol Ther, 2022. 11 (4): p. 1659-1676.DOI: 10.1007/s40120-022-00396-y. Stiefel, G. and F.M. Besag, Cardiovascular effects of methylphenidate, amphetamines and atomoxetine in the treatment of attention-deficit hyperactivity disorder. Drug Saf, 2010. 33 (10): p. 821-42.DOI: 10.2165/11536380-000000000-00000. Sullivan, M.A. and F. Rudnik-Levin, Attention deficit/hyperactivity disorder and substance abuse. Diagnostic and therapeutic considerations. Ann N Y Acad Sci, 2001. 931 : p. 251-70.DOI: 10.1111/j.1749-6632.2001.tb05783.x. Srichawla, B.S., et al., Attention Deficit Hyperactivity Disorder and Substance Use Disorder: A Narrative Review. Cureus, 2022. 14 (4): p. e24068.DOI: 10.7759/cureus.24068. Wilens, T.E., et al., Does stimulant therapy of attention-deficit/hyperactivity disorder beget later substance abuse? A meta-analytic review of the literature. Pediatrics, 2003. 111 (1): p. 179-85.DOI: 10.1542/peds.111.1.179. Volkow, N.D. and J.M. Swanson, Variables that affect the clinical use and abuse of methylphenidate in the treatment of ADHD. Am J Psychiatry, 2003. 160 (11): p. 1909-18.DOI: 10.1176/appi.ajp.160.11.1909. Carton, L., et al., What is the potential for abuse of lisdexamfetamine in adults? A preclinical and clinical literature review and expert opinion. Expert Rev Clin Pharmacol, 2022. 15 (8): p. 921-925.DOI: 10.1080/17512433.2022.2112950. Albokhari, D., et al., ALG8-CDG: Molecular and phenotypic expansion suggests clinical management guidelines. J Inherit Metab Dis, 2022. 45 (5): p. 969-980.DOI: 10.1002/jimd.12527. Kianickova, K., et al., Alterations in the Glycan Composition of Serum Glycoproteins in Attention-Deficit Hyperactivity Disorder. Int J Mol Sci, 2023. 24 (10).DOI: 10.3390/ijms24108745. Ng, B.G., et al., Biallelic Mutations in FUT8 Cause a Congenital Disorder of Glycosylation with Defective Fucosylation. Am J Hum Genet, 2018. 102 (1): p. 188- 195.DOI: 10.1016/j.ajhg.2017.12.009. Xia, Z.J., et al., The Swedish COG6-CDG experience and a comprehensive literature review. JIMD Rep, 2023. 64 (1): p. 79-89.DOI: 10.1002/jmd2.12338. Pradeep, P., H. Kang, and B. Lee, Glycosylation and behavioral symptoms in neurological disorders. Transl Psychiatry, 2023. 13 (1): p. 154.DOI: 10.1038/s41398- 023-02446-x. Paprocka, J., et al., Congenital Disorders of Glycosylation from a Neurological Perspective. Brain Sci, 2021. 11 (1).DOI: 10.3390/brainsci11010088. Karpa, K.D., et al., N-linked glycosylation is required for plasma membrane localization of D5, but not D1, dopamine receptors in transfected mammalian cells. Mol Pharmacol, 1999. 56 (5): p. 1071-8.DOI: 10.1124/mol.56.5.1071. Wu, J., et al., Role of dopamine receptors in ADHD: a systematic meta-analysis. Mol Neurobiol, 2012. 45 (3): p. 605-20.DOI: 10.1007/s12035-012-8278-5. Afonso-Oramas, D., et al., Dopamine transporter glycosylation correlates with the vulnerability of midbrain dopaminergic cells in Parkinson's disease. Neurobiol Dis, 2009. 36 (3): p. 494-508.DOI: 10.1016/j.nbd.2009.09.002. Sakai, C., [Pharmacological properties and clinical effects of the ADHD drug, Lisdexamfetamine (Vyvanse((R)) capsules 20 mg and 30 mg)]. Nihon Yakurigaku Zasshi, 2020. 155 (6): p. 413-425.DOI: 10.1254/fpj.20033. Frampton, J.E., Lisdexamfetamine: A Review in ADHD in Adults. CNS Drugs, 2016. 30 (4): p. 343-54.DOI: 10.1007/s40263-016-0327-6. Grahn, A., et al., A novel mutation on the transferrin gene abolishes one N- glycosylation site and alters the pattern of transferrin isoforms, mimicking that observed after excessive alcohol consumption. Clin Biochem, 2016. 49 (6): p. 511- 513.DOI: 10.1016/j.clinbiochem.2015.12.001. Qu, M., et al., Polymorphisms of Transferrin gene are associated with schizophrenia in Chinese Han population. J Psychiatr Res. 2008 Sep;42(11):877-83.DOI: 10.1016/j.jpsychires.2007.10.005. Demily, C. and F. Sedel, Psychiatric manifestations of treatable hereditary metabolic disorders in adults. Ann Gen Psychiatry, 2014. 13 : p. 27.DOI: 10.1186/s12991-014- 0027-x. Cannon Homaei, S., et al., ADHD symptoms in neurometabolic diseases: Underlying mechanisms and clinical implications. Neurosci Biobehav Rev, 2022. 132 : p. 838- 856.DOI: 10.1016/j.neubiorev.2021.11.012. Table 1 Table 1: Scores during diagnostic process. Psychometrics Test Score Cut-Off ASRS-V1.1. 6 minimum 4 symptoms with significant intensity ADHS-SB/HASE-SB 43 (2023) 34 (May 2024) 18 (August 2024) 18 IDA-R 8 points childhood 7 severe symptoms for inattention 8 severe symptoms for hyperactivity minimum 6 minimum 5 minimum 5 WURS-K 35 >30 BDI-II 15 14-19= mild Depression D2 Average concentration PSDI slightly signs for personality accentuation: dependent, paranoid, optimistic, selfless AQ 29 32 MWT-B IQ 94 GAF 40 (2023) 65 (2024) Range 0-100% of function Additional Declarations No competing interests reported. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-5679698","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":436167129,"identity":"30314f63-3367-4e80-85a9-2c0cfac075b5","order_by":0,"name":"Timo Jendrik 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Münster","correspondingAuthor":false,"prefix":"","firstName":"Marianne","middleName":"","lastName":"Grüneberg","suffix":""},{"id":436167134,"identity":"c027b41d-2c15-4620-a8db-03019d04263d","order_by":5,"name":"Thorsten Marquardt","email":"","orcid":"","institution":"University Hospital Münster","correspondingAuthor":false,"prefix":"","firstName":"Thorsten","middleName":"","lastName":"Marquardt","suffix":""},{"id":436167135,"identity":"7cda8ab4-4776-4298-8556-2de52c56a184","order_by":6,"name":"Daniel Kamp","email":"","orcid":"","institution":"Heinrich Heine University Düsseldorf","correspondingAuthor":false,"prefix":"","firstName":"Daniel","middleName":"","lastName":"Kamp","suffix":""},{"id":436167136,"identity":"067f58c7-865e-49c6-9eb6-2998fb389fe8","order_by":7,"name":"Leonhard Schilbach","email":"","orcid":"","institution":"University Hospital, Ludwig Maximilians University","correspondingAuthor":false,"prefix":"","firstName":"Leonhard","middleName":"","lastName":"Schilbach","suffix":""}],"badges":[],"createdAt":"2024-12-19 23:23:11","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-5679698/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-5679698/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s12888-025-06862-9","type":"published","date":"2025-04-29T15:57:02+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":79745932,"identity":"f71ddb3d-d12b-4e0a-8440-3b5ce151f397","added_by":"auto","created_at":"2025-04-02 08:50:46","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":488409,"visible":true,"origin":"","legend":"\u003cp\u003eTimeline of symptoms and diagnostic procedure.\u003c/p\u003e","description":"","filename":"floatimage2.png","url":"https://assets-eu.researchsquare.com/files/rs-5679698/v1/e1f49dbb255ee292f3c5bb78.png"},{"id":81987710,"identity":"1330c852-e319-4446-ae46-d64bbce6527e","added_by":"auto","created_at":"2025-05-05 16:05:06","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1175826,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5679698/v1/d391b108-9840-4b20-ba0f-229aaad6f6f0.pdf"},{"id":79747233,"identity":"daf27988-d110-40e4-9b25-b2c8f6c83dda","added_by":"auto","created_at":"2025-04-02 08:58:46","extension":"pdf","order_by":5,"title":"","display":"","copyAsset":false,"role":"supplement","size":987531,"visible":true,"origin":"","legend":"","description":"","filename":"CAREchecklistEnglish2013.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5679698/v1/62f38bd24251ff0ca655d59b.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"\u003cp\u003eThe long way to diagnosis: Attention Disorder, Alcohol Addiction or Congenital Disorder of Glycosylation?-A case report\u003c/p\u003e","fulltext":[{"header":"Background","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eADHD\u003c/h2\u003e \u003cp\u003eAttention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder that begins in childhood and persists into adulthood in up to 15\u0026ndash;60% of patients. Depending on the age, approximately 2\u0026ndash;5% of the population is affected by ADHD [\u003cspan additionalcitationids=\"CR2\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Core symptoms include inattentiveness, impulsivity and hyperactivity. Progressing from childhood to adulthood, hyperactivity usually turns into an inner restlessness in adults [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Moreover, patients may present with comorbidities like SUD which are very comment in ADHD and further are potentially misdiagnosed with other conditions e.g. mood disorders or personality disorders [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e] [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. According to German guidelines the diagnosis of ADHD can be made after evaluation of the clinical presentation and standardized psychometric testing [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. Standardized instrumental diagnostics is not recommended, but commonly routine blood parameters, urine toxicology screening, brain magnetic resonance imaging (MRI) and carbohydrate-deficient transferrin are used to evaluate the somatic differential diagnosis and potential substance abuse and should be taken into account before starting a medication [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. Further in case of consumption (e.g. alcohol) abstinence during the diagnostic process is important but often not possible [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e] [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. Treatment of ADHD is multimodal including psychostimulants with significant effects on symptom control, psychoeducation, psychotherapy and neurofeedback training [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e].\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003eCDT\u003c/h2\u003e \u003cp\u003eTransferrin is an iron-binding glycoprotein transporting iron throughout the human body. Carbohydrate-deficient transferrin (CDT) is mainly known as a long-term marker for alcohol abuse and describes transferrin isoforms which are deficient in their structure and appear after ethanol consumption of about 50-80g/d for more than 10\u0026ndash;15 days. As studied in 2500 individuals, the sensitivity for alcohol consumption was 82% and the specificity was 97%, respectively. The reason for the hypoglycosylation is not clear but could be an acetaldehyde-mediated inhibition of glycosyl transfer [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e10\u003c/span\u003e] [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e11\u003c/span\u003e] [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. CDT is important for assessing possible alcohol dependence and differentiating alcohol abuse from enzyme-inducing medication [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. Variations of CDT levels have been associated with pregnancy [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e14\u003c/span\u003e], fructose intolerance and galactosemia [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e15\u003c/span\u003e] and chronic obstructive pulmonary disease (COPD) [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. Further reasons for an increase in CDT could be genetic variants of transferrin, chronic active hepatitis, primary biliary cirrhosis and congenital disorders of glycosylation (CDG) [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e10\u003c/span\u003e].\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eCDG\u003c/h3\u003e\n\u003cp\u003eCDG are a heterogeneous group of genetic disorders that include various defects in the processing or synthesis of glycoproteins [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. Around 160 genetic conditions have been described commonly leading to dysfunctional hypo- or dysglycosylation of lipids and proteins [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e18\u003c/span\u003e] [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. Symptoms range from mild to severe including the failure to thrive, intellectual disability, developmental delay, facial dysmorphism, muscular hypotonia, ataxia due to cerebellar atrophy, epilepsy, liver disease, endocrinopathies, retinopathy, coagulopathy and hypoglycemia [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e21\u003c/span\u003e] Prevalence in Europe is around 0.1\u0026ndash;0.5/100000 but appears to be underdiagnosed [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. The diagnostic workup consists of a CDT screening, transferrin isoform analysis with high-performance liquid chromatography (HPLC), protein-linked glycan analysis with mass spectroscopy and genomic sequencing. Yet, biochemical pathogenesis is diverse [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e23\u003c/span\u003e] and to date, mainly four groups are distinguished: disorders of N- linked glycosylation, disorders of O-linked glycosylation, combined N- and O-linked/multiple disorders of glycosylation and lipid and glycosylphosphatidylinositol anchor biosynthesis defects [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e24\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eCDG type I affecting the glycan synthesis and CDG type II affecting glycan processing are the subdivisions of disorders of N-glycosylation [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e25\u003c/span\u003e]. The treatment depends on the exact form of CDG. Basically, three basic treatment concepts have been suggested: substrate (precursor) supplementation, cofactor supplementation and pharmacological chaperons. Further, non-causative and other treatments have been discussed [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e24\u003c/span\u003e]. For example, oral mannose can be used for mannose-6 phosphate isomerase- (MPI-) CDG, galactose for phosphoglucomutase-1- (PGM1-) CDG to increase coagulation factors and decrease serum transaminase levels, liver transplantation in MPI-CDG and coiled-coil domain containing 115- (CCDC115-) CDG, bone marrow transplantation in phosphoglucomutase-3- (PGM3-) CDG and in further variants treatment of specific symptoms like pericarditis, hypothyroidism and hypoglycemia[\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e20\u003c/span\u003e] [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e22\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe here presented case points towards interesting overlaps of ADHD symptoms, SUD and metabolic diseases.\u003c/p\u003e"},{"header":"Case Presentation","content":"\u003cp\u003eInstrumental diagnostics:\u003c/p\u003e \u003cp\u003eWritten informed consent was obtained from the patient for the publication of this case report. The CARE guidelines for case reports were followed [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e26\u003c/span\u003e]. Routine blood parameters including CDT were performed. Additionally, urine toxicology screens including ethyl glucuronide were conducted. Genetic screening for a mutation of Aldolase B gene and Transferrin gene was performed. Breath alcohol and Clinical Institute Withdrawal Assessment for Alcohol-Revised (CIWA-Ar) score was used to rule out signs of alcohol intoxication and withdrawal [\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e27\u003c/span\u003e]. Transferrin isoforms were analyzed using HPLC. Liver MRI, electrocardiogram, internal medicine consultation, abdominal ultrasound and neurological examination were additionally performed.\u003c/p\u003e \u003cp\u003ePsychometrics:\u003c/p\u003e \u003cp\u003eFor ADHD testing we used the world health organization (WHO) Adult ADHD Self-Reported Scale (ASRS-V1.1). The self-report screening questionnaire consists of 6 questions (minimum 4 questions with significant intensity required) asking for the severity of inattention, hyperactivity, and impulsivity symptoms listed in Diagnostic and Statistical Manual of Mental Disorders 4th edition (DSM-IV) [\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e28\u003c/span\u003e] and ADHS-SB/HASE-SB (ADHS- Selbstbeurteilungsbogen/Homburger ADHS-Skalen f\u0026uuml;r Erwachsene Selbstbeurteilungsbogen) self- disclosure questionnaire consisting of 18 questions (Cut-Off for significant ADHD symptoms\u0026thinsp;=\u0026thinsp;18 points) [\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e29\u003c/span\u003e] [\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e30\u003c/span\u003e] followed by a standardized interview in German language - the integrated diagnosis of ADHD in adults revised version (IDA-R) - including a semi-structured interview (9 questions on attention-deficits and 9 questions on hyperactivity, minimum 5 questions with severe symptoms required for attention-deficits and minimum 5 questions with severe symptoms required for hyperactivity) to evaluate if symptoms meet the criteria according to DSM-5 [\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e31\u003c/span\u003e]. Wender-Utah rating scale (German short version, WURS-K, 25 questions, Cut-Off for significant ADHD symptoms during childhood\u0026thinsp;\u0026ge;\u0026thinsp;30 points) was used to evaluate childhood symptoms of ADHD [\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e32\u003c/span\u003e] [\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e33\u003c/span\u003e]. Further, written teacher school reports from elementary school (grades 1\u0026ndash;4) were screened giving an impression of how the patient behaved in elementary school. Multiple Choice Word Test-B (MWT-B) consists of 37 questions and was used for the intelligence diagnostic (age validated intelligence quotient) [\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e34\u003c/span\u003e]. Becks Depression Inventory II self-report questionnaire (BDI-II) comprising 21 questions was used to evaluate symptoms of depression (0\u0026ndash;8 points\u0026thinsp;=\u0026thinsp;no depressive symptoms, 9\u0026ndash;13 points\u0026thinsp;=\u0026thinsp;minimal depressive symptoms, 14\u0026ndash;19 points\u0026thinsp;=\u0026thinsp;mild depressive symptoms, 20\u0026ndash;28 points\u0026thinsp;=\u0026thinsp;medium depressive symptoms, \u0026gt;\u0026thinsp;28 points\u0026thinsp;=\u0026thinsp;severe depressive symptoms) [\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e35\u003c/span\u003e] [\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e36\u003c/span\u003e]. D2 concentration-endurance test (D2 test, validated by age, concentration can be above average, average or below average) [\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e37\u003c/span\u003e] was used to evaluate the concentration. The German version of PSDI (Personality Styles and Disorder Inventory) consists of 140 items evaluating the non- pathological equivalents of 14 personality disorders in DSM IV and International Statistical Classification of Diseases, 10th revision, German Modification, Version 2024 (ICD-10-GM Version 2024) and was used to evaluate signs of personality accentuation (validated by age, t-values between 40\u0026ndash;60 are average) [\u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e38\u003c/span\u003e]. Autism Quotient (AQ) consists of 50 items [\u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e39\u003c/span\u003e] and was used to differentiate ADHD symptoms from possible symptoms of an autism spectrum disorder (Cut-Off for significant symptoms\u0026thinsp;\u0026ge;\u0026thinsp;32 points). Global assessment of function (GAF) was used to evaluate the general level of psychosocial functioning (Score ranges from 1 (severe impairment in psychosocial functioning) to 100 (high psychosocial functioning)) [\u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e40\u003c/span\u003e].\u003c/p\u003e \u003cp\u003e \u003cstrong\u003eCase\u003c/strong\u003e \u003cp\u003eA 30-year-old Turkish descendent, medical assistant, female patient was transferred by a psychiatrist to our specialized outpatient clinic in 2023 with symptoms of ADHD (difficulties in reading and writing, focusing, concentration, feelings of stress and permanent assessment) for completion of an ADHD diagnostic. She received no medication when she arrived at our department for the first time. The patient reported no other somatic diseases. There was no family history of severe physical or mental illnesses. The patient reported a history of depression and suspicion of ADHD, but without having received a work-up for ADHD. The patient had been on a previous medication of sertraline, escitalopram, aripiprazole, olanzapine and diazepam, but without a psychiatric inpatient treatment. Before she was put on sick leave by her general practitioner because of a somatic symptom disorder in 2021 and 2022 (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). At the time of consultation at our clinic a somatic symptom disorder could not be diagnosed. She reported symptoms of attention deficit and difficulties in focusing since her youth. School reports from elementary school (grades 1\u0026ndash;4) revealed strong symptoms of ADHD including inattention, easy distraction by other pupils, concentration difficulties, aids and additional time for tasks, problems implementing complex tasks, not targeted, inaccuracy, difficulties in writing with outlet errors. She failed her final examination in high school and had to repeat the 11th grade. During the time of consultation in our clinic the patient continued working as a medical assistant. During the diagnostic process in our outpatient clinic, she revealed the following scores in table 1:\u003c/p\u003e \u003c/p\u003e \u003cp\u003eMental status exam revealed a patient oriented to person, place and time with cooperative behavior. The motor activity revealed some psychomotor agitation and some fidgeting with her hands. The attention span was reduced and the concentration was mildly impaired. The thought form was diffuse. The affect was appropriate. The mood was euthymic. The thought content was normal. The patient denied suicidal or homicidal ideations. Neurological examination was unremarkable.\u003c/p\u003e \u003cp\u003eIn total the diagnosis of ADHD combined type was made according to the German guidelines for ADHD, the European consensus statement and ICD-10-GM Version 2024 without comorbidities like depression, autism, personality disorders, psychotic disorders or somatic symptom disorders according to ICD-10 [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e] [\u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e41\u003c/span\u003e] [\u003cspan citationid=\"CR43\" class=\"CitationRef\"\u003e42\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eIn parallel before starting ADHD-medication routine blood parameters including blood cell count, coagulation, liver enzymes, kidney parameters, electrolytes and thyroid parameters were normal. Monocytes were slightly increased to 10.8% on the 22nd of June 2023, 11.4% on the 28th of July and 10.8% (2.0-9.5) on the 10th of August 2023. Lactate dehydrogenase (LDH) was 288 U/l (\u0026lt;\u0026thinsp;250) on the 28th of July 2023. Immunofixation was negative. Anti-nuclear antibodies (ANA), anti-mitochondrial antibodies (AMA), anti-soluble liver antigen antibodies (SLA), liver kidney microsome antibodies (LKM), anti-smooth muscle antibodies (ASMA), cytoplasmic anti-neutrophil cytoplasmic antibodies (c-ANCA), perinuclear ANCA (p-ANCA) were all negative. Atypical ANCA (X-ANCA) were 1:32 (1:\u0026lt;10). Serum protein electrophoresis was negative. Beta 1 globulin was 4,6% (4,9\u0026thinsp;\u0026minus;\u0026thinsp;7,2). Transferrin was 1,65 g/l (1.80\u0026ndash;3.82) and ferritin was 47,7% (16\u0026ndash;45%) on the 28th of July 2023.\u003c/p\u003e \u003cp\u003eAn unusually high CDT of 19.6% (\u0026lt;\u0026thinsp;1,3%) was found on the 23rd of June 2023 followed by 19,1% on the 27th of June 2023 and 23,2% on the 10th of August 2023. Yet, urine ethyl glucuronide was negative (\u0026lt;\u0026thinsp;0,5 mg/l) on the 14th of July 2023 and 10th of August 2023, repeatedly indicated absence of alcohol intake. Urine toxicology screening was also negative for opioids, cannabinoids, amphetamines and cocaine on the 27th of June 2023, 28th of July 2023 and 10th of August 2023. Breath alcohol and CIWA-Ar score was negative on the 27th of July and 28th of July. The anamnesis by the husband also was not suggestive of addiction. In conclusion, after repeated consultations with the patient and her husband and consistent laboratory results, alcohol addiction was ruled out. Pregnancy test was negative on the 27th of June 2023.\u003c/p\u003e \u003cp\u003eIn parallel, because of the high CDT transferrin isoforms were analyzed using HPLC and revealed high Disialo-Transferrin of (22,8% (\u0026lt;\u0026thinsp;1,8%)) and low Tetrasialo-Transferrin (70% (\u0026gt;\u0026thinsp;85%)). Other parameters revealed 0.0% of Monosialo-Transferrin (0.0%), 2,4% of Trisialo-Transferrin (\u0026lt;\u0026thinsp;6.5%), and 4,8% of Pentasialo-Transferrin (\u0026lt;\u0026thinsp;15%) respectively, pointing towards evidence for a congenital disorder of glycosylation.\u003c/p\u003e \u003cp\u003eAdditionally, genetic testing ruled out hereditary fructose intolerance, a known cause of transferrin hypoglycosylation. Native liver MRI-scan was normal; the patient rejected receiving contrast agent. Abdominal ultrasound and internal medicine consultation were negative for any abdominal and internal medicine abnormalities. Electrocardiogram was normal. An additional MRI scan of the brain was rejected by the patient.\u003c/p\u003e \u003cp\u003eAfter extensive diagnostic procedures in August 2023, partially retarded methylphenidate was started with 5mg/day and increased up to 10 mg/day and later 15 mg/day. This was not well tolerated, and the patient reported headache, agitation and nausea so that the medication was changed to lisdexamfetamine in a dosis of 30 mg/day due to mentioned side effects. The dosis was increased to 50 and later on to 70 mg/day by the beginning of 2024. Symptoms decreased and the patient felt better during the day. Drug levels revealed 104 ng/ml amphetamines (20\u0026ndash;100 ng/ml) in the blood on the 29th of May 2024 and symptom scores in the ADHS-SB decreased (from 43 in 2023 to 34 in May 2024 and 18 in August 2024). Further, GAF improved from 40 in 2023 (Burdened by psychosocial stress related to work) to 65 in 2024 (Improvement at work, finished exam at work) (table 1).\u003c/p\u003e \u003cp\u003eSince the patient improved with lisdexamfetamine but still reported symptoms a further diagnostic and therapy regarding CDG was recommended but rejected by the patient. The patient wanted to postpone the decision of further diagnostic into the future if symptoms remain.\u003c/p\u003e \u003cp\u003eIn May 2024 transferrin analysis revealed the heterozygous transferrin mutation c.1295A\u0026thinsp;\u0026gt;\u0026thinsp;G that destroys the glycosylation site at the asparagine 432. The amino acid changes due to the mutation as well as the lack of glycan at this site were confirmed by mass spectrometry. Thus, transferrin in the patient has only one glycosylation site left and the hypoglycosylation is not indicative of CDG disease.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eIn this case we report a young female patient who initially presented with symptoms of ADHD. The case is unique because of the following reasons:\u003c/p\u003e \u003cp\u003e \u003col\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003eThe abnormally high serum CDT was initially considered as a likely indicator for an overlap with a possible alcohol dependence.\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003eStigmatization of psychiatric patients due to false positive biomarkers.\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003eThese findings led to a delayed start of the ADHD therapy because of the more complex differential diagnosis for rare causes of elevated CDT.\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003eDiagnostic/Treatment of ADHD and co-morbid substance abuse.\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003eCo-existing ADHD together with CDG (which was suspected in first place) and possible role of glycosylation related to ADHD.\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003eLisdexamfetamine was a good treatment option in this case of ADHD.\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003eComplex possible metabolic and genetic findings in psychiatric disorders.\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003c/ol\u003e \u003c/p\u003e\n\u003ch3\u003eReason 1–4: Problems of co-existing ADHD and SUD:\u003c/h3\u003e\n\u003cp\u003eThe complex situation of ADHD and SUD includes the problems of an adequate diagnostic under possible substance abuse. It can be discussed that during the diagnostic procedure in cases of addiction a first screening for ADHD symptoms can be done but complete testing should be performed after withdrawal cause intoxication and withdrawal symptoms can mimic ADHD symptoms [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e] [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. Further, the treatment with a substance like methylphenidate and lisdexamfetamine (psychostimulants) potentially is discussed to be misused in e.g. 5\u0026ndash;35% of cases in high school students and college students and abuse and diversion potential can be discussed. Further, additionally effects on the cardiovascular system like mild increase in blood pressure and heart rate need to be discussed and are important if further psychiatric and somatic comorbidities exist [\u003cspan citationid=\"CR44\" class=\"CitationRef\"\u003e43\u003c/span\u003e] [\u003cspan citationid=\"CR45\" class=\"CitationRef\"\u003e44\u003c/span\u003e] [\u003cspan citationid=\"CR46\" class=\"CitationRef\"\u003e45\u003c/span\u003e] [\u003cspan citationid=\"CR47\" class=\"CitationRef\"\u003e46\u003c/span\u003e]. These facts have to be taken into account if in parallel a continued intake of another substance due to an abuse exist which further might complicate the therapy [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. In conclusion, a close screening and monitoring of ADHD medication use is recommended [\u003cspan citationid=\"CR45\" class=\"CitationRef\"\u003e44\u003c/span\u003e]. Around 50% of patients with ADHD have SUD and the role of \u0026ldquo;self-medicated\u0026rdquo; ADHD symptoms can be discussed. The SUD therapy can suffer under a not treated ADHD and ongoing substance abuse can limit the ADHD therapy. The use of non-stimulant pharmacotherapy needs to be discussed for cases of ADHD and SUD [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e] [\u003cspan citationid=\"CR48\" class=\"CitationRef\"\u003e47\u003c/span\u003e]. Interestingly, psychostimulants are discussed to reduce risky behavior like substance abuse among patients with ADHD and prevent the development of SUD, but physicians often are not sure about the exact treatment of patients presenting with ADHD and substance abuse at the same time [\u003cspan citationid=\"CR49\" class=\"CitationRef\"\u003e48\u003c/span\u003e]. In a meta- analysis comparing follow up studies the use of psychostimulants in childhood was related to a reduction in the risk for drug and alcohol addiction later in life [\u003cspan citationid=\"CR50\" class=\"CitationRef\"\u003e49\u003c/span\u003e]. Further, different administration (e.g. oral, intravenous) revealed that orally intake of methylphenidate constrains abuse [\u003cspan citationid=\"CR51\" class=\"CitationRef\"\u003e50\u003c/span\u003e]. Further, the occurrence of e.g. possible lisdexamfetamine abuse has been discussed but the concerns could not be substantiated in patients [\u003cspan citationid=\"CR53\" class=\"CitationRef\"\u003e51\u003c/span\u003e].\u003c/p\u003e \u003cp\u003e \u003cem\u003eReason 5: Co-existing ADHD together with CDG (which was suspected in first place) and possible role of glycosylation related to ADHD\u003c/em\u003e:\u003c/p\u003e \u003cp\u003eTo date, only few cases have linked abnormal glycosylation to attention disorders including ADHD. For example, alpha-1,3-glucosyltransferase- (ALG8-) CDG has been found to show intellectual disabilities besides other organ manifestations including musculoskeletal, dermatologic and cardiac symptoms [\u003cspan citationid=\"CR54\" class=\"CitationRef\"\u003e52\u003c/span\u003e]. Further, alterations of glycan composition of glycoproteins were found in patients with ADHD and it was discussed that these alterations are connected to further findings of patients with the diagnosis of CDG and changes in behavior and neurological activity and variants in fucosyltransferase 8 (FUT8) at the same time [\u003cspan citationid=\"CR55\" class=\"CitationRef\"\u003e53\u003c/span\u003e] [\u003cspan citationid=\"CR56\" class=\"CitationRef\"\u003e54\u003c/span\u003e]. Another case with Conserved Oligomeric Golgi (COG-)CDG was reported to include symptoms of ADHD in the clinical presentation [\u003cspan citationid=\"CR57\" class=\"CitationRef\"\u003e55\u003c/span\u003e]. Taken together the exact pathomechanism of symptoms of ADHD occurring together with a possible CDG is not clear. However, the association may be overlooked if standard serum markers such as liver enzymes show normal serum levels or in patients with overlapping substance abuse. Previously, neurodevelopmental disorders such as autism have been described in CDG. Further N-glycosylation abnormalities were described in ADHD [\u003cspan citationid=\"CR58\" class=\"CitationRef\"\u003e56\u003c/span\u003e, \u003cspan citationid=\"CR59\" class=\"CitationRef\"\u003e57\u003c/span\u003e]. Concerning the here described symptoms of ADHD together with a suspected occurrence of CDG at the same time one mechanism of pathology can be a missing N-linked glycosylation which is important for the membrane localization of the dopamine D5 receptor [\u003cspan citationid=\"CR60\" class=\"CitationRef\"\u003e58\u003c/span\u003e]. This receptor was discussed to be important in ADHD [\u003cspan citationid=\"CR61\" class=\"CitationRef\"\u003e59\u003c/span\u003e]. Further, contradicting glycosylation of the dopamine transporter (DAT) is more efficiently in transporting dopamine and was discussed to be involved in the vulnerability of midbrain dopamine cells in Parkinson\u0026rsquo;s disease [\u003cspan citationid=\"CR62\" class=\"CitationRef\"\u003e60\u003c/span\u003e]. Since dopamine and DAT are one therapeutical target in ADHD treatment this could be one possible mechanism when considering ADHD and CDG at the same time.\u003c/p\u003e \u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003eReason 6: Lisdexamfetamine was a good treatment option in this case of ADHD:\u003c/h2\u003e \u003cp\u003eIn the present case, treatment with methylphenidate was not well tolerated. Lisdexamfetamine was a good alternative option and the patient reported symptom relief with 30 mg and later 70 mg. Lisdexamfetamine is a long-acting amfetamine prodrug and approved by the FDA (US Food and Drug Administration) and EMA (European Medicine Agency) for ADHD in adults inhibiting the dopamine and noradrenaline transporters, inhibiting the transmitter reuptake and increasing the dopamine and noradrenaline release by being taken up into neuronal cells and acting on the vesicular monoamine transporters [\u003cspan citationid=\"CR63\" class=\"CitationRef\"\u003e61\u003c/span\u003e] [\u003cspan citationid=\"CR64\" class=\"CitationRef\"\u003e62\u003c/span\u003e] [\u003cspan citationid=\"CR53\" class=\"CitationRef\"\u003e51\u003c/span\u003e]. Comparable cases using lisdexamfetamine have not been reported before.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eReason 7: Complex possible metabolic and genetic findings in psychiatric disorders:\u003c/h3\u003e\n\u003cp\u003eIn the end the diagnosis of a CDG was not likely due to the finding of a transferrin mutation which was previously described in a healthy patient [\u003cspan citationid=\"CR65\" class=\"CitationRef\"\u003e63\u003c/span\u003e]. Polymorphisms in the transferrin gene have been found in patients with schizophrenia and were discussed to affect oligodendrocytes and myelin formation but the role in ADHD remains unclear [\u003cspan citationid=\"CR66\" class=\"CitationRef\"\u003e64\u003c/span\u003e]. Even if no clear evidence for a metabolic disorder was found it can be discussed as a reason for the development of psychiatric symptoms like in ADHD [\u003cspan citationid=\"CR67\" class=\"CitationRef\"\u003e65\u003c/span\u003e] [\u003cspan citationid=\"CR68\" class=\"CitationRef\"\u003e66\u003c/span\u003e]. Lastly, it is not clear what effect the found transferrin mutation might have concerning psychiatric symptoms and what other findings could have been made concerning metabolic diseases. The found mutation can be discussed as an incidental finding.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThis work refers to a case report but points towards problems of ADHD treatment in an outpatient clinic and overlaps with a possible SUD. A delayed start of medication was found in this case due to abnormal high biomarkers (CDT). Firstly, the patient rejected further diagnostic or treatment for the here found glycosylation abnormalities (possible CDG) and was satisfied with lisdexamfetamine due to an improvement with the therapy, but it needs to be discussed that in cases of metabolic disorders psychiatric symptoms can occur. Secondly, the later found transferrin mutation points towards a genetic case and the effects on psychiatric symptoms due to these findings are not clear. Further, we consider CDT as an important diagnostic tool in patients with ADHD because (beside relevance in alcohol consumption) overlaps with glycosylation abnormalities are possible. Lastly, the patient rejected to do a brain MRI scan, but the diagnosis of ADHD could be made based on extensive laboratory diagnostics and the lack of a clear recommendation for a brain MRI scan in the ADHD guidelines.\u003c/p\u003e \u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003eLimitations\u003c/h2\u003e \u003cp\u003eDue to a case report, there is a lack of generalizability. A confounding factor is the here described transferrin mutation which could be further discussed as a stigmatization for the patient regarding consumption of alcohol (high CDT). Missing further metabolic and genetic tests could have been useful to evaluate if the mentioned transferrin mutation is really affecting central nervous structures leading to symptoms of ADHD.\u003c/p\u003e \u003c/div\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eADHD: attention\u0026nbsp;deficit\u0026nbsp;hyperactivity disorder\u003c/p\u003e\n\u003cp\u003eADHS: Aufmerksamkeitsdefizit-/Hyperaktivit\u0026auml;tsst\u0026ouml;rung\u0026nbsp;ADHS-SB: ADHS-Selbstbeurteilungsbogen\u003c/p\u003e\n\u003cp\u003eALG8:\u0026nbsp;alpha-1,3-glucosyltransferase AMA:\u0026nbsp;anti-mitochondrial antibodies ANA:\u0026nbsp;Anti-nuclear antibodies\u003c/p\u003e\n\u003cp\u003eAQ:\u0026nbsp;Autism\u0026nbsp;Quotient\u003c/p\u003e\n\u003cp\u003eASMA:\u0026nbsp;anti-smooth\u0026nbsp;muscle\u0026nbsp;antibodies\u003c/p\u003e\n\u003cp\u003eASRS-V1.1:\u0026nbsp;Adult\u0026nbsp;ADHD\u0026nbsp;Self-Reported\u0026nbsp;Scale\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;BDI-II: Becks Depression Inventory II\u003c/p\u003e\n\u003cp\u003ec-ANCA:\u0026nbsp;cytoplasmic\u0026nbsp;anti-neutrophil\u0026nbsp;cytoplasmic\u0026nbsp;antibodies CCDC115: coiled-coil domain containing 115\u003c/p\u003e\n\u003cp\u003eCDG:\u0026nbsp;congenital\u0026nbsp;disorder\u0026nbsp;of\u0026nbsp;glycosylation CDT: carbohydrate-deficient transferrin\u003c/p\u003e\n\u003cp\u003eCIWA-Ar:\u0026nbsp;Clinical\u0026nbsp;Institute\u0026nbsp;Withdrawal\u0026nbsp;Assessment\u0026nbsp;for\u0026nbsp;Alcohol-Revised COG: Conserved Oligomeric Golgi\u003c/p\u003e\n\u003cp\u003eCOPD:\u0026nbsp;chronic\u0026nbsp;obstructive\u0026nbsp;pulmonary\u0026nbsp;disease\u0026nbsp;DAT: dopamine transporter\u003c/p\u003e\n\u003cp\u003eDSM-IV:\u0026nbsp;Diagnostic\u0026nbsp;and\u0026nbsp;Statistical\u0026nbsp;Manual\u0026nbsp;of\u0026nbsp;Mental\u0026nbsp;Disorders 4\u003csup\u003eth\u003c/sup\u003e edition D2 test:\u0026nbsp;D2 concentration-endurance test\u003c/p\u003e\n\u003cp\u003eEMA: European Medicine Agency\u0026nbsp;FDA:\u0026nbsp;US Food and Drug Administration FUT8: fucosyltransferase 8\u003c/p\u003e\n\u003cp\u003eHASE-SB:\u0026nbsp;Homburger\u0026nbsp;ADHS-Skalen\u0026nbsp;f\u0026uuml;r\u0026nbsp;Erwachsene\u0026nbsp;Selbstbeurteilungsbogen HPLC:\u0026nbsp;high-performance liquid chromatography\u003c/p\u003e\n\u003cp\u003eICD-10-GM\u0026nbsp;Version\u0026nbsp;2024:\u0026nbsp;International\u0026nbsp;Statistical\u0026nbsp;Classification\u0026nbsp;of\u0026nbsp;Diseases,\u0026nbsp;10\u003csup\u003eth\u003c/sup\u003e revision,\u0026nbsp;German Modification, Version 2024\u003c/p\u003e\n\u003cp\u003eIDA-R:\u0026nbsp;integrated\u0026nbsp;diagnosis\u0026nbsp;of\u0026nbsp;ADHD\u0026nbsp;in\u0026nbsp;adults\u0026nbsp;revised\u0026nbsp;version LDH: lactate dehydrogenase\u003c/p\u003e\n\u003cp\u003eLKM:\u0026nbsp;liver\u0026nbsp;kidney\u0026nbsp;microsome\u0026nbsp;antibodies MPI: mannose-6 phosphate isomerase MRI: magnetic resonance imaging\u003c/p\u003e\n\u003cp\u003eMWT-B:\u0026nbsp;Multiple\u0026nbsp;Choice\u0026nbsp;Word\u0026nbsp;Test-B\u003c/p\u003e\n\u003cp\u003ep-ANCA:\u0026nbsp;perinuclear\u0026nbsp;anti-neutrophil\u0026nbsp;cytoplasmic\u0026nbsp;antibodies PGM1: phosphoglucomutase-1\u003c/p\u003e\n\u003cp\u003ePGM3:\u0026nbsp;phosphoglucomutase-3\u003c/p\u003e\n\u003cp\u003ePSDI:\u0026nbsp;Personality\u0026nbsp;Styles\u0026nbsp;and\u0026nbsp;Disorder\u0026nbsp;Inventory SLA: anti-soluble liver antigen antibodies\u003c/p\u003e\n\u003cp\u003eSUD: substance-use disorders WHO:\u0026nbsp;world\u0026nbsp;health\u0026nbsp;organization\u003c/p\u003e\n\u003cp\u003eWURS-K: Wender-Utah rating scale german short version X-ANCA: atypical anti-neutrophil cytoplasmic antibodies\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003eEthics Approval\u003c/p\u003e\n\u003cp\u003eEthical approval was not required for case reports.\u003c/p\u003e\n\u003cp\u003eConsent to participate\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003eConsent for publication\u003c/p\u003e\n\u003cp\u003eWritten informed consent was obtained from the patient for the publication of this case report.\u003c/p\u003e\n\u003cp\u003eCompeting interests\u003c/p\u003e\n\u003cp\u003eThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.\u003c/p\u003e\n\u003cp\u003eFunding\u003c/p\u003e\n\u003cp\u003eDoes not apply.\u003c/p\u003e\n\u003cp\u003eAvailability of data and materials\u003c/p\u003e\n\u003cp\u003eData is provided within the manuscript or supplementary information files.\u003c/p\u003e\n\u003cp\u003eAcknowledgments\u003c/p\u003e\n\u003cp\u003eNot applicable\u003c/p\u003e\n\u003cp\u003eAuthor Contributions\u003c/p\u003e\n\u003cp\u003eTJF: Writing \u0026ndash; original draft, Conceptualization, Data Curation, Project administration, Figure preparation. LH: Writing \u0026ndash; review \u0026amp; editing, Data Curation. AB: Writing \u0026ndash; review \u0026amp; editing. YW: Writing \u0026ndash; review \u0026amp; editing. MG: Data Curation. TM: Writing \u0026ndash; review \u0026amp; editing, Data Curation. DK: Writing \u0026ndash; review \u0026amp; editing, LS: Writing \u0026ndash; review \u0026amp; editing.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n \u003cli\u003eSimon, V., et al., \u003cem\u003ePrevalence and correlates of adult attention-deficit hyperactivity disorder: meta-analysis.\u0026nbsp;\u003c/em\u003eBr J Psychiatry, 2009. \u003cstrong\u003e194\u003c/strong\u003e(3): p. 204-11.DOI: 10.1192/bjp.bp.107.048827.\u003c/li\u003e\n \u003cli\u003eKessler, R.C., et al., \u003cem\u003eThe prevalence and correlates of adult ADHD in the United States: results from the National Comorbidity Survey Replication.\u0026nbsp;\u003c/em\u003eAm J Psychiatry, 2006. \u003cstrong\u003e163\u003c/strong\u003e(4): p. 716-23.DOI: 10.1176/ajp.2006.163.4.716.\u003c/li\u003e\n \u003cli\u003eFaraone, S.V., J. Biederman, and E. 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Diagnostic and therapeutic considerations.\u0026nbsp;\u003c/em\u003eAnn N Y Acad Sci, 2001. \u003cstrong\u003e931\u003c/strong\u003e: p. 251-70.DOI: 10.1111/j.1749-6632.2001.tb05783.x.\u003c/li\u003e\n \u003cli\u003eSrichawla, B.S., et al., \u003cem\u003eAttention Deficit Hyperactivity Disorder and Substance Use Disorder: A Narrative Review.\u0026nbsp;\u003c/em\u003eCureus, 2022. \u003cstrong\u003e14\u003c/strong\u003e(4): p. e24068.DOI: 10.7759/cureus.24068.\u003c/li\u003e\n \u003cli\u003eWilens, T.E., et al., \u003cem\u003eDoes stimulant therapy of attention-deficit/hyperactivity disorder beget later substance abuse? A meta-analytic review of the literature.\u0026nbsp;\u003c/em\u003ePediatrics, 2003. \u003cstrong\u003e111\u003c/strong\u003e(1): p. 179-85.DOI: 10.1542/peds.111.1.179.\u003c/li\u003e\n \u003cli\u003eVolkow, N.D. and J.M. Swanson, \u003cem\u003eVariables that affect the clinical use and abuse of methylphenidate in the treatment of ADHD.\u0026nbsp;\u003c/em\u003eAm J Psychiatry, 2003. \u003cstrong\u003e160\u003c/strong\u003e(11): p. 1909-18.DOI: 10.1176/appi.ajp.160.11.1909.\u003c/li\u003e\n \u003cli\u003eCarton, L., et al., \u003cem\u003eWhat is the potential for abuse of lisdexamfetamine in adults? A preclinical and clinical literature review and expert opinion.\u0026nbsp;\u003c/em\u003eExpert Rev Clin Pharmacol, 2022. \u003cstrong\u003e15\u003c/strong\u003e(8): p. 921-925.DOI: 10.1080/17512433.2022.2112950.\u003c/li\u003e\n \u003cli\u003eAlbokhari, D., et al., \u003cem\u003eALG8-CDG: Molecular and phenotypic expansion suggests clinical management guidelines.\u0026nbsp;\u003c/em\u003eJ Inherit Metab Dis, 2022. \u003cstrong\u003e45\u003c/strong\u003e(5): p. 969-980.DOI: 10.1002/jimd.12527.\u003c/li\u003e\n \u003cli\u003eKianickova, K., et al., \u003cem\u003eAlterations in the Glycan Composition of Serum Glycoproteins in Attention-Deficit Hyperactivity Disorder.\u0026nbsp;\u003c/em\u003eInt J Mol Sci, 2023. \u003cstrong\u003e24\u003c/strong\u003e(10).DOI: 10.3390/ijms24108745.\u003c/li\u003e\n \u003cli\u003eNg, B.G., et al., \u003cem\u003eBiallelic Mutations in FUT8 Cause a Congenital Disorder of Glycosylation with Defective Fucosylation.\u0026nbsp;\u003c/em\u003eAm J Hum Genet, 2018. \u003cstrong\u003e102\u003c/strong\u003e(1): p. 188- 195.DOI: 10.1016/j.ajhg.2017.12.009.\u003c/li\u003e\n \u003cli\u003eXia, Z.J., et al., \u003cem\u003eThe Swedish COG6-CDG experience and a comprehensive literature review.\u0026nbsp;\u003c/em\u003eJIMD Rep, 2023. \u003cstrong\u003e64\u003c/strong\u003e(1): p. 79-89.DOI: 10.1002/jmd2.12338.\u003c/li\u003e\n \u003cli\u003ePradeep, P., H. Kang, and B. Lee, \u003cem\u003eGlycosylation and behavioral symptoms in neurological disorders.\u0026nbsp;\u003c/em\u003eTransl Psychiatry, 2023. \u003cstrong\u003e13\u003c/strong\u003e(1): p. 154.DOI: 10.1038/s41398- 023-02446-x.\u003c/li\u003e\n \u003cli\u003ePaprocka, J., et al., \u003cem\u003eCongenital Disorders of Glycosylation from a Neurological Perspective.\u0026nbsp;\u003c/em\u003eBrain Sci, 2021. \u003cstrong\u003e11\u003c/strong\u003e(1).DOI: 10.3390/brainsci11010088.\u003c/li\u003e\n \u003cli\u003eKarpa, K.D., et al., \u003cem\u003eN-linked glycosylation is required for plasma membrane localization of D5, but not D1, dopamine receptors in transfected mammalian cells.\u0026nbsp;\u003c/em\u003eMol Pharmacol, 1999. \u003cstrong\u003e56\u003c/strong\u003e(5): p. 1071-8.DOI: 10.1124/mol.56.5.1071.\u003c/li\u003e\n \u003cli\u003eWu, J., et al., \u003cem\u003eRole of dopamine receptors in ADHD: a systematic meta-analysis.\u0026nbsp;\u003c/em\u003eMol Neurobiol, 2012. \u003cstrong\u003e45\u003c/strong\u003e(3): p. 605-20.DOI: 10.1007/s12035-012-8278-5.\u003c/li\u003e\n \u003cli\u003eAfonso-Oramas, D., et al., \u003cem\u003eDopamine transporter glycosylation correlates with the vulnerability of midbrain dopaminergic cells in Parkinson\u0026apos;s disease.\u0026nbsp;\u003c/em\u003eNeurobiol Dis, 2009. \u003cstrong\u003e36\u003c/strong\u003e(3): p. 494-508.DOI: 10.1016/j.nbd.2009.09.002.\u003c/li\u003e\n \u003cli\u003eSakai, C., \u003cem\u003e[Pharmacological properties and clinical effects of the ADHD drug, Lisdexamfetamine (Vyvanse((R)) capsules 20 mg and 30 mg)].\u0026nbsp;\u003c/em\u003eNihon Yakurigaku Zasshi, 2020. \u003cstrong\u003e155\u003c/strong\u003e(6): p. 413-425.DOI: 10.1254/fpj.20033.\u003c/li\u003e\n \u003cli\u003eFrampton, J.E., \u003cem\u003eLisdexamfetamine: A Review in ADHD in Adults.\u0026nbsp;\u003c/em\u003eCNS Drugs, 2016. \u003cstrong\u003e30\u003c/strong\u003e(4): p. 343-54.DOI: 10.1007/s40263-016-0327-6.\u003c/li\u003e\n \u003cli\u003eGrahn, A., et al., \u003cem\u003eA novel mutation on the transferrin gene abolishes one N- glycosylation site and alters the pattern of transferrin isoforms, mimicking that observed after excessive alcohol consumption.\u0026nbsp;\u003c/em\u003eClin Biochem, 2016. \u003cstrong\u003e49\u003c/strong\u003e(6): p. 511- 513.DOI: 10.1016/j.clinbiochem.2015.12.001.\u003c/li\u003e\n \u003cli\u003eQu, M., et al., Polymorphisms of Transferrin gene are associated with schizophrenia in Chinese Han population. J Psychiatr Res. 2008 Sep;42(11):877-83.DOI: 10.1016/j.jpsychires.2007.10.005.\u003c/li\u003e\n \u003cli\u003eDemily, C. and F. Sedel, \u003cem\u003ePsychiatric manifestations of treatable hereditary metabolic disorders in adults.\u0026nbsp;\u003c/em\u003eAnn Gen Psychiatry, 2014. \u003cstrong\u003e13\u003c/strong\u003e: p. 27.DOI: 10.1186/s12991-014- 0027-x.\u003c/li\u003e\n \u003cli\u003eCannon Homaei, S., et al., \u003cem\u003eADHD symptoms in neurometabolic diseases: Underlying mechanisms and clinical implications.\u0026nbsp;\u003c/em\u003eNeurosci Biobehav Rev, 2022. \u003cstrong\u003e132\u003c/strong\u003e: p. 838- 856.DOI: 10.1016/j.neubiorev.2021.11.012.\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Table 1","content":"\u003cp\u003eTable 1: Scores during diagnostic process.\u003c/p\u003e\u003cp\u003ePsychometrics\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 20.3642%;\"\u003e\n \u003cp\u003eTest\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 42.2185%;\"\u003e\n \u003cp\u003eScore\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 37.4172%;\"\u003e\n \u003cp\u003eCut-Off\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 20.3642%;\"\u003e\n \u003cp\u003eASRS-V1.1.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 42.2185%;\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 37.4172%;\"\u003e\n \u003cp\u003eminimum 4 symptoms with significant intensity\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 20.3642%;\"\u003e\n \u003cp\u003eADHS-SB/HASE-SB\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 42.2185%;\"\u003e\n \u003cp\u003e43 (2023)\u003c/p\u003e\n \u003cp\u003e34 (May 2024)\u003c/p\u003e\n \u003cp\u003e18 (August 2024)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 37.4172%;\"\u003e\n \u003cp\u003e18\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 20.3642%;\"\u003e\n \u003cp\u003eIDA-R\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 42.2185%;\"\u003e\n \u003cp\u003e8 points childhood\u003c/p\u003e\n \u003cp\u003e7 severe symptoms for inattention\u003c/p\u003e\n \u003cp\u003e8 severe symptoms for hyperactivity\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 37.4172%;\"\u003e\n \u003cp\u003eminimum 6\u003c/p\u003e\n \u003cp\u003eminimum 5\u003c/p\u003e\n \u003cp\u003eminimum 5\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 20.3642%;\"\u003e\n \u003cp\u003eWURS-K\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 42.2185%;\"\u003e\n \u003cp\u003e35\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 37.4172%;\"\u003e\n \u003cp\u003e\u0026gt;30\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 20.3642%;\"\u003e\n \u003cp\u003eBDI-II\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 42.2185%;\"\u003e\n \u003cp\u003e15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 37.4172%;\"\u003e\n \u003cp\u003e14-19= mild Depression\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 20.3642%;\"\u003e\n \u003cp\u003eD2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 42.2185%;\"\u003e\n \u003cp\u003eAverage concentration\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 37.4172%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 20.3642%;\"\u003e\n \u003cp\u003ePSDI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 42.2185%;\"\u003e\n \u003cp\u003eslightly signs for personality accentuation: dependent, paranoid, optimistic, selfless\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 37.4172%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 20.3642%;\"\u003e\n \u003cp\u003eAQ\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 42.2185%;\"\u003e\n \u003cp\u003e29\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 37.4172%;\"\u003e\n \u003cp\u003e32\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 20.3642%;\"\u003e\n \u003cp\u003eMWT-B\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 42.2185%;\"\u003e\n \u003cp\u003eIQ 94\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 37.4172%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 20.3642%;\"\u003e\n \u003cp\u003eGAF\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 42.2185%;\"\u003e\n \u003cp\u003e40 (2023)\u003c/p\u003e\n \u003cp\u003e65 (2024)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 37.4172%;\"\u003e\n \u003cp\u003eRange 0-100% of function\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-psychiatry","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bpsy","sideBox":"Learn more about [BMC Psychiatry](http://bmcpsychiatry.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bpsy/default.aspx","title":"BMC Psychiatry","twitterHandle":"@BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"ADHD, CDT, CDG, case report, psychostimulants","lastPublishedDoi":"10.21203/rs.3.rs-5679698/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5679698/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eAttention deficit hyperactivity disorder (ADHD) is a relatively common disorder in clinical psychiatry. Patients often suffer from symptoms long before the diagnosis due to an overlap with other psychiatric differential diagnosis. Importantly, alcohol addiction and other illicit drug dependence and withdrawal symptoms mimicking ADHD symptoms should be ruled out. Here we present a rare case of a young female patient with symptoms of ADHD and an extremely high carbohydrate-deficient transferrin (CDT) of 19,6% (\u0026lt;\u0026thinsp;1,3%) indicating the presence of a congenital disorder of glycosylation (CDG). A thorough diagnostic workup excluded alcohol addiction as a cause of the constantly high CDT levels. The CDT test was positive due a transferrin mutation affecting the glycosylation site. Nevertheless, psychiatric symptoms can be due to metabolic disorders which should be considered. Further, substance-use disorders (SUD) are a critical and potentially complicated differential diagnosis concerning diagnostic procedures and treatment in ADHD.\u003c/p\u003e","manuscriptTitle":"The long way to diagnosis: Attention Disorder, Alcohol Addiction or Congenital Disorder of Glycosylation?-A case report","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-04-02 08:50:41","doi":"10.21203/rs.3.rs-5679698/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Accepted","date":"2025-04-15T03:16:39+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-04-14T09:16:43+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"291442251508956152086508130925537694595","date":"2025-03-31T07:17:41+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-03-31T06:55:37+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-03-29T10:48:06+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Psychiatry","date":"2025-03-28T15:45:28+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-psychiatry","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bpsy","sideBox":"Learn more about [BMC Psychiatry](http://bmcpsychiatry.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bpsy/default.aspx","title":"BMC Psychiatry","twitterHandle":"@BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"ea7abbbc-2738-4a75-8501-ae55d9077078","owner":[],"postedDate":"April 2nd, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2025-05-05T16:00:09+00:00","versionOfRecord":{"articleIdentity":"rs-5679698","link":"https://doi.org/10.1186/s12888-025-06862-9","journal":{"identity":"bmc-psychiatry","isVorOnly":false,"title":"BMC Psychiatry"},"publishedOn":"2025-04-29 15:57:02","publishedOnDateReadable":"April 29th, 2025"},"versionCreatedAt":"2025-04-02 08:50:41","video":"","vorDoi":"10.1186/s12888-025-06862-9","vorDoiUrl":"https://doi.org/10.1186/s12888-025-06862-9","workflowStages":[]},"version":"v1","identity":"rs-5679698","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-5679698","identity":"rs-5679698","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}