An incidental heterozygous ATP7B nonsense variant leading to a diagnostic pitfall for Wilson disease: a pediatric case report

An incidental heterozygous ATP7B nonsense variant leading to a diagnostic pitfall for Wilson disease: a pediatric 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 An incidental heterozygous ATP7B nonsense variant leading to a diagnostic pitfall for Wilson disease: a pediatric case report Zhongqiang Xu, Junfeng Tang This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8649506/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 12 You are reading this latest preprint version Abstract Background Wilson disease (WD) is an autosomal recessive disorder caused by pathogenic variants in ATP7B, resulting in impaired copper transport and progressive copper accumulation, most prominently affecting the liver. With the growing use of genetic testing, incidental detection of ATP7B pathogenic/likely pathogenic variants in individuals without typical hepatic phenotypes can prompt overdiagnosis and unnecessary investigations. This case highlights the importance of interpreting a single heterozygous ATP7B variant in the context of phenotype and a standardized biochemical diagnostic pathway for WD. Case presentation A 13-year-old boy presented with brief paroxysmal attacks for >1 year, markedly worsened over the preceding month. Episodes were triggered by rising from sitting, characterized by transient postural instability with unilateral head deviation and ipsilateral dystonic/choreiform movements, lasted ~10 seconds, and resolved spontaneously. Consciousness was preserved, with no incontinence, convulsions, or postictal symptoms. Interictal neurological examination was normal. Ambulatory EEG monitoring captured three typical attacks without epileptiform discharges or ictal EEG correlates, and brain MRI was unremarkable. A slit-lamp examination revealed no Kayser–Fleischer ring. A low serum copper level (9.43 μmol/L; reference 10.50–29.90) prompted further evaluation; genetic testing incidentally identified a heterozygous ATP7B variant (NM_000053.4:c.2851C>T; p.Gln951Ter), reported as likely pathogenic. WD was considered. However, ceruloplasmin was normal (231.6 mg/L; reference 200.0–420.0), copper oxidase was normal (0.372 OD; >0.200), liver biochemistry was normal (ALT 11 U/L, AST 16 U/L, GGT 14 U/L; bilirubin within reference range), and abdominal ultrasound showed a normal liver and biliary tree. Urinary copper was reported as not elevated (quantitative 24-h value not available). Overall, findings did not support WD. Conclusions This case illustrates a diagnostic pitfall: incidental heterozygous ATP7B nonsense variants may lead to anchoring bias toward WD in individuals without hepatic phenotypes. WD diagnosis should rely on integrated clinical and standardized copper-metabolism evidence, avoiding attribution based on genetics or a single biochemical abnormality alone. Wilson disease ATP7B incidental finding diagnostic pitfall copper metabolism child case report Background Wilson disease (WD) is an autosomal recessive disorder caused by pathogenic variants in ATP7B, encoding a copper-transporting P-type ATPase essential for biliary copper excretion and systemic copper homeostasis. Copper accumulation may lead to hepatic, neurological, or mixed presentations, and diagnosis requires integration of phenotype, copper-related biomarkers, and supportive clinical/imaging findings. 1 – 3 With increasing access to clinical genetic testing, ATP7B variants may be identified incidentally in individuals lacking typical WD manifestations. Interpreting such findings without a standardized diagnostic framework can lead to overdiagnosis and unnecessary evaluations, particularly when key biochemical evidence is absent. 4 Here, we describe a child with paroxysmal movement attacks in whom an incidental heterozygous ATP7B truncating variant and a single low serum copper measurement prompted concern for WD, but subsequent evaluation supported a non-WD interpretation. Case presentation A 13-year-old boy presented with recurrent brief attacks for more than 1 year, with increased frequency in the month prior to admission. Episodes were consistently triggered by standing up after sitting, featuring transient postural instability accompanied by unilateral head deviation and ipsilateral involuntary movements described as dystonic/choreiform. Each episode lasted approximately 10 seconds and resolved spontaneously. He remained fully conscious throughout, without urinary/fecal incontinence, convulsive activity, or postictal drowsiness. In the month before presentation, attacks increased to dozens per day, impairing school performance. Appetite, sleep, bowel and bladder habits were normal, with no weight loss. Past medical history was unremarkable. Family history included consanguinity in grandparents and an uncle with epilepsy. Vital signs were stable (T 36.5°C, P 86/min, R 19/min, BP 129/79 mmHg); weight was 53 kg. There was no jaundice, no hepatosplenomegaly, no abdominal pain, and no bleeding tendency. Interictal neurological examination was normal. Slit-lamp examination showed no Kayser–Fleischer ring. To evaluate epileptic and structural etiologies, Ambulatory EEG captured three typical attacks, with no epileptiform discharges or ictal EEG correlates, and brain MRI was normal, including the basal ganglia. A biochemical evaluation revealed low serum copper (9.43 µmol/L; reference 10.50–29.90, flame atomic absorption). Genetic testing was performed using an XY Paroxysmal Movement Disorders panel based on targeted capture and next-generation sequencing (NGS), which identified a heterozygous ATP7B nonsense variant (NM_000053.4:c.2851C > T; p.Gln951Ter). A WD-focused work-up showed normal ceruloplasmin (231.6 mg/L; reference 200.0–420.0, immunoturbidimetry) and normal copper oxidase (0.372 OD; >0.200, p-phenylenediamine method). Liver biochemistry was normal (ALT 11 U/L, AST 16 U/L, direct bilirubin 4.5 µmol/L, indirect bilirubin 6.3 µmol/L, GGT 14 U/L). Abdominal ultrasound demonstrated a normal liver (normal size and contour, homogeneous echotexture, normal intrahepatic vasculature), no biliary dilatation (CBD ~ 4 mm), and an incidental gallbladder polypoid lesion (~ 4×3 mm). Urinary copper testing was reported by the laboratory as ‘not elevated’, but the report did not provide a quantitative 24-hour urinary copper value (unit/reference range not available). Therefore, this result could not be used for quantitative interpretation. For symptom control, oxcarbazepine 0.15 g twice daily reduced attack frequency. Pharmacogenetic testing showed HLA-B*15:02 heterozygosity, implying increased risk of severe cutaneous adverse reactions associated with carbamazepine/oxcarbazepine; therefore, on 28 November, therapy was switched to levetiracetam 0.5 g twice daily for risk management. At telephone follow-up 2 months later, attacks decreased to 0–1 per day, markedly improved from baseline. A timeline of the clinical course, investigations, and management is summarized in Table 1 . [Insert Table 1 here] Table 1 Timeline of clinical course, investigation, and management Date Event / Investigation Key findings / Notes 2024-11 (approx.) Symptom onset (patient-reported) Kinesigenic attacks on rising from sitting; unilateral dystonic/choreiform movements; ~10 s; awareness preserved. 2025-10 (approx.) Symptom escalation (patient-reported) Frequency increased to dozens/day; impaired school performance. 2025-11-20 Event/Investigation: Ambulatory EEG (dynamic EEG) Three typical attacks captured; no epileptiform discharges or ictal EEG changes (no electroclinical seizure). 2025-11-23 Treatment started Oxcarbazepine 0.15 g BID; attacks improved. 2025-11-28 Pharmacogenetic result HLA-B*15:02 heterozygous; increased SCAR risk with carbamazepine/oxcarbazepine. 2025-11-28 Treatment adjustment / discharge Switched to levetiracetam 0.5 g BID (risk management). 2025-12-12 Genetic panel report issued XY paroxysmal movement disorders panel (targeted capture NGS): ATP7B NM_000053.4:c.2851C > T (p.Gln951Ter), heterozygous; reported as likely pathogenic; WD considered. 2025-12-13 Copper/liver work-up for suspected WD Serum copper 9.43 µmol/L. Ceruloplasmin and copper oxidase normal. Urinary copper: reported 'not elevated' (no quantitative 24-h value). Liver biochemistry normal. Abdominal ultrasound: normal liver/biliary tree; incidental gallbladder polyp (~ 4×3 mm). 2025-12-13 Specialist consultation Tertiary referral center review: no evidence supporting WD ('not suggestive of WD'). 2025-12-14 Ophthalmologic examination Slit-lamp: no Kayser-Fleischer ring. 2026-01-16 Follow-up (telephone) Attacks decreased to 0–1/day vs baseline; no rash reported. Notes : Approximate dates are based on patient/guardian report. Abbreviations: EEG, electroencephalogram; MRI, magnetic resonance imaging; WD, Wilson disease; NGS, next-generation sequencing; BID, twice daily; SCAR, severe cutaneous adverse reactions. Discussion and conclusions Despite detection of a heterozygous truncating ATP7B variant and a single low serum copper measurement, this patient lacked supportive evidence for WD: normal ceruloplasmin, normal copper oxidase, normal liver enzymes and bilirubin, no Kayser–Fleischer ring, and normal liver ultrasound findings. 1 , 2 Ambulatory EEG recorded three habitual events without ictal EEG correlates, which reduced the likelihood of epileptic seizures and supported a paroxysmal movement disorder phenotype. Under the Leipzig scoring system, the estimated score was 1, attributable solely to ATP7B variant detection (+ 1); Kayser–Fleischer ring (0), typical WD neurological features (0), ceruloplasmin (0), hepatic signs/biochemistry (0), and brain MRI basal ganglia changes (0). A quantitative 24-hour urinary copper value was unavailable and therefore could not be scored, attributable only to ATP7B variant detection, while other supportive clinical/biochemical features were absent. 3 Although a quantitative 24-hour urinary copper value was not available, the overall clinical and biochemical profile—normal ceruloplasmin, normal liver biochemistry, absence of Kayser–Fleischer rings, and normal abdominal ultrasound—collectively argued against WD. 1,2 Importantly, WD is autosomal recessive; therefore, a single heterozygous ATP7B truncating variant in the absence of a compatible hepatic phenotype and key biochemical abnormalities is more appropriately interpreted as carrier status or an incidental finding, rather than diagnostic of WD. Genetic information should be integrated with a standardized diagnostic pathway to avoid anchoring bias and overdiagnosis. 4 This case also underscores the limited specificity of total serum copper as a standalone diagnostic marker. Total serum copper is strongly influenced by ceruloplasmin and can be low in non-WD contexts. When ceruloplasmin is normal and urinary copper is not elevated, a single low serum copper level should not drive a diagnosis of WD. 1,5 Clinically, he had no liver-related symptoms or signs, including jaundice, hepatosplenomegaly, abdominal pain, or bleeding tendency, further lowering the likelihood of WD. Although the clinical phenotype was more consistent with paroxysmal kinesigenic dyskinesia (PKD)—brief kinesigenic attacks with preserved awareness and normal interictal examinations—our report focuses on the WD diagnostic pitfall triggered by incidental ATP7B findings. 6 Pharmacogenetic information (HLA-B*15:02) appropriately informed risk management for oxcarbazepine/carbamazepine-associated severe cutaneous adverse reactions and supported switching to an alternative agent. 7 – 10 Conclusion: Incidental detection of a heterozygous ATP7B nonsense variant, particularly alongside a single nonspecific biochemical abnormality, can misdirect clinicians toward WD. A structured diagnostic approach—centered on phenotype and standardized copper-metabolism evidence—helps prevent overdiagnosis and unnecessary interventions. Limitations First, a quantitative 24-hour urinary copper value (with unit and reference range) was unavailable; only a qualitative laboratory statement (‘not elevated’) was provided, limiting quantitative interpretation and formal Leipzig scoring. Second, follow-up was limited to 2 months. Abbreviations Approximate dates are based on patient/guardian report. Abbreviations: EEG, electroencephalogram; MRI, magnetic resonance imaging; WD, Wilson disease; NGS, next-generation sequencing; BID, twice daily; SCAR, severe cutaneous adverse reactions. Declarations Ethics approval and consent to participate Ethics approval was obtained from the Institutional Review Board/Ethics Committee of The Second Affiliated Hospital of Wannan Medical College, or the requirement for ethics approval was waived because this is a single case report. Consent for publication Written informed consent for publication was obtained from the patient’s legal guardian(s). Where appropriate, assent was also obtained from the patient. Competing interests The authors declare no potential conflict of interest. Funding None. Author Contribution Zhongqiang Xu conceived and designed the study and drafted the manuscript. Junfeng Tang contributed to data interpretation and critically revised the manuscript. Both authors approved the final version. Acknowledgements None Data Availability Not applicable. References Schilsky ML, et al. A multidisciplinary approach to the diagnosis and management of Wilson disease: 2022 Practice Guidance on Wilson disease from the American Association for the Study of Liver Diseases. Hepatology. 2025;82:E41–90. https://doi.org/10.1002/hep.32801 . European Association for Study of, L. EASL Clinical Practice Guidelines. Wilson's disease. J Hepatol. 2012;56:671–85. https://doi.org/10.1016/j.jhep.2011.11.007 . Ferenci P, et al. Diagnosis and phenotypic classification of Wilson disease. Liver Int. 2003;23:139–42. https://doi.org/10.1034/j.1600-0676.2003.00824.x . Stattermayer AF, et al. The dilemma to diagnose Wilson disease by genetic testing alone. Eur J Clin Invest. 2019;49:e13147. https://doi.org/10.1111/eci.13147 . Czlonkowska A, et al. Wilson disease. Nat Rev Dis Primers. 2018;4:21. https://doi.org/10.1038/s41572-018-0018-3 . Bruno MK, et al. Clinical evaluation of idiopathic paroxysmal kinesigenic dyskinesia: new diagnostic criteria. Neurology. 2004;63:2280–7. https://doi.org/10.1212/01.wnl.0000147298.05983.50 . Phillips EJ, et al. Clinical Pharmacogenetics Implementation Consortium Guideline forHLAGenotype and Use of Carbamazepine and Oxcarbazepine: 2017 Update. Clin Pharmacol Ther. 2018;103:574–81. https://doi.org/10.1002/cpt.1004 . Tangamornsuksan W, Scholfield N, Lohitnavy M. Association Between HLA genotypes and Oxcarbazepine-induced Cutaneous Adverse Drug Reactions: A Systematic Review and Meta-Analysis. J Pharm Pharm Sci. 2018;21:1–18. https://doi.org/10.18433/J36S7D . Chen P, et al. Carbamazepine-induced toxic effects and HLA-B*1502 screening in Taiwan. N Engl J Med. 2011;364:1126–33. https://doi.org/10.1056/NEJMoa1009717 . Tiwattanon K, et al. Implementation of HLA-B*15:02 Genotyping as Standard-of-Care for Reducing Carbamazepine/Oxcarbazepine Induced Cutaneous Adverse Drug Reactions in Thailand. Front Pharmacol. 2022;13. https://doi.org/10.3389/fphar.2022.867490 . Additional Declarations No competing interests reported. Cite Share Download PDF Status: Under Review Version 1 posted Editorial decision: Revision requested 05 Apr, 2026 Reviews received at journal 03 Mar, 2026 Reviews received at journal 20 Feb, 2026 Reviewers agreed at journal 19 Feb, 2026 Reviews received at journal 17 Feb, 2026 Reviewers agreed at journal 17 Feb, 2026 Reviewers agreed at journal 17 Feb, 2026 Reviewers invited by journal 17 Feb, 2026 Editor invited by journal 27 Jan, 2026 Editor assigned by journal 26 Jan, 2026 Submission checks completed at journal 26 Jan, 2026 First submitted to journal 20 Jan, 2026 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. 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-8649506","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":592838540,"identity":"75ba86ca-987f-4453-a57f-542434b9cc4b","order_by":0,"name":"Zhongqiang Xu","email":"","orcid":"","institution":"The Second Affiliated Hospital of Wannan Medical College","correspondingAuthor":false,"prefix":"","firstName":"Zhongqiang","middleName":"","lastName":"Xu","suffix":""},{"id":592838542,"identity":"7c78f18a-1f38-411a-989e-019274085864","order_by":1,"name":"Junfeng Tang","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA9UlEQVRIiWNgGAWjYLCCByCCmf/hgw8MEkRqSUgAEuw8zIYzSNPCz8MmzUOMav7Z7RcfJP6wy5N35j1sbPPHIo+/gfnhoxt4tEjcOVNskJCQXGx4mC/xcW6bRLHEATZj4xx81tzISZNISGBO3NjMYGyc2yCR2HAA6EJ8WuRv5KT/SEioB2kxk7b4I5E4n5AWgxvpx4DeP5w4n5nHTJqBTSJxAyEthjdymCUS0o4nbmBmSzbsbZNI3HiYgF/kbqQ//PDBpjpxfv/hgw9+/KlLnHe8+eFjvN5n4DGAuPAATIAZr3IQYH8ApuQbCKocBaNgFIyCkQoAk/tPNQa+aLsAAAAASUVORK5CYII=","orcid":"","institution":"The Second Affiliated Hospital of Wannan Medical College","correspondingAuthor":true,"prefix":"","firstName":"Junfeng","middleName":"","lastName":"Tang","suffix":""}],"badges":[],"createdAt":"2026-01-20 13:15:29","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-8649506/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-8649506/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":103050164,"identity":"29650dfa-b717-4a5e-9d1b-cdeaef745cfe","added_by":"auto","created_at":"2026-02-20 07:48:34","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":388850,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8649506/v1/9ddab9a6-ad8f-442e-8d11-cf3a11bf440b.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"An incidental heterozygous ATP7B nonsense variant leading to a diagnostic pitfall for Wilson disease: a pediatric case report","fulltext":[{"header":"Background","content":"\u003cp\u003eWilson disease (WD) is an autosomal recessive disorder caused by pathogenic variants in ATP7B, encoding a copper-transporting P-type ATPase essential for biliary copper excretion and systemic copper homeostasis. Copper accumulation may lead to hepatic, neurological, or mixed presentations, and diagnosis requires integration of phenotype, copper-related biomarkers, and supportive clinical/imaging findings.\u003csup\u003e\u003cspan additionalcitationids=\"CR2\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eWith increasing access to clinical genetic testing, ATP7B variants may be identified incidentally in individuals lacking typical WD manifestations. Interpreting such findings without a standardized diagnostic framework can lead to overdiagnosis and unnecessary evaluations, particularly when key biochemical evidence is absent.\u003csup\u003e\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eHere, we describe a child with paroxysmal movement attacks in whom an incidental heterozygous ATP7B truncating variant and a single low serum copper measurement prompted concern for WD, but subsequent evaluation supported a non-WD interpretation.\u003c/p\u003e"},{"header":"Case presentation","content":"\u003cp\u003eA 13-year-old boy presented with recurrent brief attacks for more than 1 year, with increased frequency in the month prior to admission. Episodes were consistently triggered by standing up after sitting, featuring transient postural instability accompanied by unilateral head deviation and ipsilateral involuntary movements described as dystonic/choreiform. Each episode lasted approximately 10 seconds and resolved spontaneously. He remained fully conscious throughout, without urinary/fecal incontinence, convulsive activity, or postictal drowsiness. In the month before presentation, attacks increased to dozens per day, impairing school performance. Appetite, sleep, bowel and bladder habits were normal, with no weight loss.\u003c/p\u003e \u003cp\u003ePast medical history was unremarkable. Family history included consanguinity in grandparents and an uncle with epilepsy. Vital signs were stable (T 36.5°C, P 86/min, R 19/min, BP 129/79 mmHg); weight was 53 kg. There was no jaundice, no hepatosplenomegaly, no abdominal pain, and no bleeding tendency. Interictal neurological examination was normal. Slit-lamp examination showed no Kayser–Fleischer ring.\u003c/p\u003e \u003cp\u003eTo evaluate epileptic and structural etiologies, Ambulatory EEG captured three typical attacks, with no epileptiform discharges or ictal EEG correlates, and brain MRI was normal, including the basal ganglia.\u003c/p\u003e \u003cp\u003eA biochemical evaluation revealed low serum copper (9.43 µmol/L; reference 10.50–29.90, flame atomic absorption). Genetic testing was performed using an XY Paroxysmal Movement Disorders panel based on targeted capture and next-generation sequencing (NGS), which identified a heterozygous ATP7B nonsense variant (NM_000053.4:c.2851C \u0026gt; T; p.Gln951Ter). A WD-focused work-up showed normal ceruloplasmin (231.6 mg/L; reference 200.0–420.0, immunoturbidimetry) and normal copper oxidase (0.372 OD; \u0026gt;0.200, p-phenylenediamine method). Liver biochemistry was normal (ALT 11 U/L, AST 16 U/L, direct bilirubin 4.5 µmol/L, indirect bilirubin 6.3 µmol/L, GGT 14 U/L). Abdominal ultrasound demonstrated a normal liver (normal size and contour, homogeneous echotexture, normal intrahepatic vasculature), no biliary dilatation (CBD ~ 4 mm), and an incidental gallbladder polypoid lesion (~ 4×3 mm). Urinary copper testing was reported by the laboratory as ‘not elevated’, but the report did not provide a quantitative 24-hour urinary copper value (unit/reference range not available). Therefore, this result could not be used for quantitative interpretation.\u003c/p\u003e \u003cp\u003eFor symptom control, oxcarbazepine 0.15 g twice daily reduced attack frequency. Pharmacogenetic testing showed HLA-B*15:02 heterozygosity, implying increased risk of severe cutaneous adverse reactions associated with carbamazepine/oxcarbazepine; therefore, on 28 November, therapy was switched to levetiracetam 0.5 g twice daily for risk management. At telephone follow-up 2 months later, attacks decreased to 0–1 per day, markedly improved from baseline.\u003c/p\u003e \u003cp\u003eA timeline of the clinical course, investigations, and management is summarized in Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e. [Insert Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e here]\u003c/p\u003e \u003cp\u003e \u003c/p\u003e\u003cdiv class=\"gridtable\"\u003e\u003cdiv align=\"left\" class=\"colspec\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\"\u003e\u003c/div\u003e\u003ctable id=\"Tab1\" border=\"1\"\u003e \u003ccaption\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eTimeline of clinical course, investigation, and management\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"3\"\u003e \u003c/colgroup\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\"\u003e \u003cp\u003eDate\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\"\u003e \u003cp\u003eEvent / Investigation\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\"\u003e \u003cp\u003eKey findings / Notes\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\"\u003e \u003cp\u003e2024-11 (approx.)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\"\u003e \u003cp\u003eSymptom onset (patient-reported)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\"\u003e \u003cp\u003eKinesigenic attacks on rising from sitting; unilateral dystonic/choreiform movements; ~10 s; awareness preserved.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\"\u003e \u003cp\u003e2025-10 (approx.)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\"\u003e \u003cp\u003eSymptom escalation (patient-reported)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\"\u003e \u003cp\u003eFrequency increased to dozens/day; impaired school performance.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\"\u003e \u003cp\u003e2025-11-20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\"\u003e \u003cp\u003eEvent/Investigation: Ambulatory EEG (dynamic EEG)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\"\u003e \u003cp\u003eThree typical attacks captured; no epileptiform discharges or ictal EEG changes (no electroclinical seizure).\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\"\u003e \u003cp\u003e2025-11-23\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\"\u003e \u003cp\u003eTreatment started\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\"\u003e \u003cp\u003eOxcarbazepine 0.15 g BID; attacks improved.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\"\u003e \u003cp\u003e2025-11-28\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\"\u003e \u003cp\u003ePharmacogenetic result\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\"\u003e \u003cp\u003eHLA-B*15:02 heterozygous; increased SCAR risk with carbamazepine/oxcarbazepine.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\"\u003e \u003cp\u003e2025-11-28\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\"\u003e \u003cp\u003eTreatment adjustment / discharge\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\"\u003e \u003cp\u003eSwitched to levetiracetam 0.5 g BID (risk management).\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\"\u003e \u003cp\u003e2025-12-12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\"\u003e \u003cp\u003eGenetic panel report issued\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\"\u003e \u003cp\u003eXY paroxysmal movement disorders panel (targeted capture NGS): ATP7B NM_000053.4:c.2851C \u0026gt; T (p.Gln951Ter), heterozygous; reported as likely pathogenic; WD considered.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\"\u003e \u003cp\u003e2025-12-13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\"\u003e \u003cp\u003eCopper/liver work-up for suspected WD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\"\u003e \u003cp\u003eSerum copper 9.43 µmol/L. Ceruloplasmin and copper oxidase normal. Urinary copper: reported 'not elevated' (no quantitative 24-h value). Liver biochemistry normal. Abdominal ultrasound: normal liver/biliary tree; incidental gallbladder polyp (~ 4×3 mm).\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\"\u003e \u003cp\u003e2025-12-13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\"\u003e \u003cp\u003eSpecialist consultation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\"\u003e \u003cp\u003eTertiary referral center review: no evidence supporting WD ('not suggestive of WD').\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\"\u003e \u003cp\u003e2025-12-14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\"\u003e \u003cp\u003eOphthalmologic examination\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\"\u003e \u003cp\u003eSlit-lamp: no Kayser-Fleischer ring.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\"\u003e \u003cp\u003e2026-01-16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\"\u003e \u003cp\u003eFollow-up (telephone)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\"\u003e \u003cp\u003eAttacks decreased to 0–1/day vs baseline; no rash reported.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"3\"\u003e\u003cb\u003eNotes\u003c/b\u003e: Approximate dates are based on patient/guardian report. Abbreviations: EEG, electroencephalogram; MRI, magnetic resonance imaging; WD, Wilson disease; NGS, next-generation sequencing; BID, twice daily; SCAR, severe cutaneous adverse reactions.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003cp\u003e\u003c/p\u003e \n\n"},{"header":"Discussion and conclusions","content":"\u003cp\u003eDespite detection of a heterozygous truncating ATP7B variant and a single low serum copper measurement, this patient lacked supportive evidence for WD: normal ceruloplasmin, normal copper oxidase, normal liver enzymes and bilirubin, no Kayser–Fleischer ring, and normal liver ultrasound findings.\u003csup\u003e\u003cspan class=\"CitationRef\"\u003e1\u003c/span\u003e,\u003cspan class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e Ambulatory EEG recorded three habitual events without ictal EEG correlates, which reduced the likelihood of epileptic seizures and supported a paroxysmal movement disorder phenotype. Under the Leipzig scoring system, the estimated score was 1, attributable solely to ATP7B variant detection (+ 1); Kayser–Fleischer ring (0), typical WD neurological features (0), ceruloplasmin (0), hepatic signs/biochemistry (0), and brain MRI basal ganglia changes (0). A quantitative 24-hour urinary copper value was unavailable and therefore could not be scored, attributable only to ATP7B variant detection, while other supportive clinical/biochemical features were absent.\u003csup\u003e\u003cspan class=\"CitationRef\"\u003e3\u003c/span\u003e\u003c/sup\u003e Although a quantitative 24-hour urinary copper value was not available, the overall clinical and biochemical profile—normal ceruloplasmin, normal liver biochemistry, absence of Kayser–Fleischer rings, and normal abdominal ultrasound—collectively argued against WD. \u003csup\u003e1,2\u003c/sup\u003e\u003c/p\u003e\u003cp\u003eImportantly, WD is autosomal recessive; therefore, a single heterozygous ATP7B truncating variant in the absence of a compatible hepatic phenotype and key biochemical abnormalities is more appropriately interpreted as carrier status or an incidental finding, rather than diagnostic of WD. Genetic information should be integrated with a standardized diagnostic pathway to avoid anchoring bias and overdiagnosis.\u003csup\u003e\u003cspan class=\"CitationRef\"\u003e4\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e\u003cp\u003eThis case also underscores the limited specificity of total serum copper as a standalone diagnostic marker. Total serum copper is strongly influenced by ceruloplasmin and can be low in non-WD contexts. When ceruloplasmin is normal and urinary copper is not elevated, a single low serum copper level should not drive a diagnosis of WD.\u003csup\u003e1,5\u003c/sup\u003e Clinically, he had no liver-related symptoms or signs, including jaundice, hepatosplenomegaly, abdominal pain, or bleeding tendency, further lowering the likelihood of WD.\u003c/p\u003e\u003cp\u003eAlthough the clinical phenotype was more consistent with paroxysmal kinesigenic dyskinesia (PKD)—brief kinesigenic attacks with preserved awareness and normal interictal examinations—our report focuses on the WD diagnostic pitfall triggered by incidental ATP7B findings.\u003csup\u003e\u003cspan class=\"CitationRef\"\u003e6\u003c/span\u003e\u003c/sup\u003e Pharmacogenetic information (HLA-B*15:02) appropriately informed risk management for oxcarbazepine/carbamazepine-associated severe cutaneous adverse reactions and supported switching to an alternative agent.\u003csup\u003e\u003cspan class=\"CitationRef\"\u003e7\u003c/span\u003e–\u003cspan class=\"CitationRef\"\u003e10\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e\u003cp\u003eConclusion: Incidental detection of a heterozygous ATP7B nonsense variant, particularly alongside a single nonspecific biochemical abnormality, can misdirect clinicians toward WD. A structured diagnostic approach—centered on phenotype and standardized copper-metabolism evidence—helps prevent overdiagnosis and unnecessary interventions.\u003c/p\u003e\u003ch3\u003eLimitations\u003c/h3\u003e\u003cp\u003eFirst, a quantitative 24-hour urinary copper value (with unit and reference range) was unavailable; only a qualitative laboratory statement (‘not elevated’) was provided, limiting quantitative interpretation and formal Leipzig scoring. Second, follow-up was limited to 2 months.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eApproximate dates are based on patient/guardian report. Abbreviations: EEG, electroencephalogram; MRI, magnetic resonance imaging; WD, Wilson disease; NGS, next-generation sequencing; BID, twice daily; SCAR, severe cutaneous adverse reactions.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e \u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e \u003cp\u003e Ethics approval was obtained from the Institutional Review Board/Ethics Committee of The Second Affiliated Hospital of Wannan Medical College, or the requirement for ethics approval was waived because this is a single case report.\u003c/p\u003e \u003c/p\u003e \u003cp\u003e \u003cstrong\u003eConsent for publication\u003c/strong\u003e \u003cp\u003e Written informed consent for publication was obtained from the patient\u0026rsquo;s legal guardian(s). Where appropriate, assent was also obtained from the patient.\u003c/p\u003e \u003c/p\u003e \u003cp\u003e \u003cstrong\u003eCompeting interests\u003c/strong\u003e \u003cp\u003eThe authors declare no potential conflict of interest.\u003c/p\u003e \u003c/p\u003e\u003ch2\u003eFunding\u003c/h2\u003e \u003cp\u003eNone.\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eZhongqiang Xu conceived and designed the study and drafted the manuscript. Junfeng Tang contributed to data interpretation and critically revised the manuscript. Both authors approved the final version.\u003c/p\u003e\u003ch2\u003eAcknowledgements\u003c/h2\u003e \u003cp\u003eNone\u003c/p\u003e\u003ch2\u003eData Availability\u003c/h2\u003e\u003cp\u003eNot applicable.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eSchilsky ML, et al. A multidisciplinary approach to the diagnosis and management of Wilson disease: 2022 Practice Guidance on Wilson disease from the American Association for the Study of Liver Diseases. Hepatology. 2025;82:E41\u0026ndash;90. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1002/hep.32801\u003c/span\u003e\u003cspan address=\"10.1002/hep.32801\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eEuropean Association for Study of, L. EASL Clinical Practice Guidelines. Wilson's disease. J Hepatol. 2012;56:671\u0026ndash;85. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/j.jhep.2011.11.007\u003c/span\u003e\u003cspan address=\"10.1016/j.jhep.2011.11.007\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFerenci P, et al. Diagnosis and phenotypic classification of Wilson disease. Liver Int. 2003;23:139\u0026ndash;42. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1034/j.1600-0676.2003.00824.x\u003c/span\u003e\u003cspan address=\"10.1034/j.1600-0676.2003.00824.x\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eStattermayer AF, et al. The dilemma to diagnose Wilson disease by genetic testing alone. Eur J Clin Invest. 2019;49:e13147. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1111/eci.13147\u003c/span\u003e\u003cspan address=\"10.1111/eci.13147\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCzlonkowska A, et al. Wilson disease. Nat Rev Dis Primers. 2018;4:21. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1038/s41572-018-0018-3\u003c/span\u003e\u003cspan address=\"10.1038/s41572-018-0018-3\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBruno MK, et al. Clinical evaluation of idiopathic paroxysmal kinesigenic dyskinesia: new diagnostic criteria. Neurology. 2004;63:2280\u0026ndash;7. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1212/01.wnl.0000147298.05983.50\u003c/span\u003e\u003cspan address=\"10.1212/01.wnl.0000147298.05983.50\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePhillips EJ, et al. Clinical Pharmacogenetics Implementation Consortium Guideline forHLAGenotype and Use of Carbamazepine and Oxcarbazepine: 2017 Update. Clin Pharmacol Ther. 2018;103:574\u0026ndash;81. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1002/cpt.1004\u003c/span\u003e\u003cspan address=\"10.1002/cpt.1004\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTangamornsuksan W, Scholfield N, Lohitnavy M. Association Between HLA genotypes and Oxcarbazepine-induced Cutaneous Adverse Drug Reactions: A Systematic Review and Meta-Analysis. J Pharm Pharm Sci. 2018;21:1\u0026ndash;18. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.18433/J36S7D\u003c/span\u003e\u003cspan address=\"10.18433/J36S7D\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChen P, et al. Carbamazepine-induced toxic effects and HLA-B*1502 screening in Taiwan. N Engl J Med. 2011;364:1126\u0026ndash;33. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1056/NEJMoa1009717\u003c/span\u003e\u003cspan address=\"10.1056/NEJMoa1009717\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTiwattanon K, et al. Implementation of HLA-B*15:02 Genotyping as Standard-of-Care for Reducing Carbamazepine/Oxcarbazepine Induced Cutaneous Adverse Drug Reactions in Thailand. Front Pharmacol. 2022;13. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.3389/fphar.2022.867490\u003c/span\u003e\u003cspan address=\"10.3389/fphar.2022.867490\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-gastroenterology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bmge","sideBox":"Learn more about [BMC Gastroenterology](http://bmcgastroenterol.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bmge/default.aspx","title":"BMC Gastroenterology","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Wilson disease, ATP7B, incidental finding, diagnostic pitfall, copper metabolism, child, case report","lastPublishedDoi":"10.21203/rs.3.rs-8649506/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8649506/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWilson disease (WD) is an autosomal recessive disorder caused by pathogenic variants in ATP7B, resulting in impaired copper transport and progressive copper accumulation, most prominently affecting the liver. With the growing use of genetic testing, incidental detection of ATP7B pathogenic/likely pathogenic variants in individuals without typical hepatic phenotypes can prompt overdiagnosis and unnecessary investigations. This case highlights the importance of interpreting a single heterozygous ATP7B variant in the context of phenotype and a standardized biochemical diagnostic pathway for WD.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCase presentation\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA 13-year-old boy presented with brief paroxysmal attacks for \u0026gt;1 year, markedly worsened over the preceding month. Episodes were triggered by rising from sitting, characterized by transient postural instability with unilateral head deviation and ipsilateral dystonic/choreiform movements, lasted ~10 seconds, and resolved spontaneously. Consciousness was preserved, with no incontinence, convulsions, or postictal symptoms. Interictal neurological examination was normal. Ambulatory EEG monitoring captured three typical attacks without epileptiform discharges or ictal EEG correlates, and brain MRI was unremarkable. A slit-lamp examination revealed no Kayser–Fleischer ring.\u003c/p\u003e\n\u003cp\u003eA low serum copper level (9.43 μmol/L; reference 10.50–29.90) prompted further evaluation; genetic testing incidentally identified a heterozygous ATP7B variant (NM_000053.4:c.2851C\u0026gt;T; p.Gln951Ter), reported as likely pathogenic. WD was considered. However, ceruloplasmin was normal (231.6 mg/L; reference 200.0–420.0), copper oxidase was normal (0.372 OD; \u0026gt;0.200), liver biochemistry was normal (ALT 11 U/L, AST 16 U/L, GGT 14 U/L; bilirubin within reference range), and abdominal ultrasound showed a normal liver and biliary tree. Urinary copper was reported as not elevated (quantitative 24-h value not available). Overall, findings did not support WD.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis case illustrates a diagnostic pitfall: incidental heterozygous ATP7B nonsense variants may lead to anchoring bias toward WD in individuals without hepatic phenotypes. WD diagnosis should rely on integrated clinical and standardized copper-metabolism evidence, avoiding attribution based on genetics or a single biochemical abnormality alone.\u003c/p\u003e","manuscriptTitle":"An incidental heterozygous ATP7B nonsense variant leading to a diagnostic pitfall for Wilson disease: a pediatric case report","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-02-19 14:47:12","doi":"10.21203/rs.3.rs-8649506/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2026-04-05T14:35:50+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-03-03T20:55:32+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-02-20T17:48:08+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"253563560825518635474765205650256600650","date":"2026-02-19T13:16:35+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-02-17T15:32:21+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"282942644841085294813842394371693321099","date":"2026-02-17T15:02:19+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"64826185435041134564524393589912470811","date":"2026-02-17T13:08:24+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-02-17T09:22:48+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2026-01-27T07:09:48+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-01-26T13:47:44+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-01-26T13:43:39+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Gastroenterology","date":"2026-01-20T12:21:32+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-gastroenterology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bmge","sideBox":"Learn more about [BMC Gastroenterology](http://bmcgastroenterol.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bmge/default.aspx","title":"BMC Gastroenterology","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"f5f088a8-a0a9-4d57-9454-4ecac5429b11","owner":[],"postedDate":"February 19th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-05-07T12:23:51+00:00","versionOfRecord":[],"versionCreatedAt":"2026-02-19 14:47:12","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8649506","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8649506","identity":"rs-8649506","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}