{"paper_id":"273a3e94-7f1f-4b07-8d9d-cd689f3755e7","body_text":"A Rare Case of Down Syndrome with Severe Pancytopenia: Clinical Analysis and Literature Review | 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 A Rare Case of Down Syndrome with Severe Pancytopenia: Clinical Analysis and Literature Review Ying Zheng, Wenjun Yue, Dehong Gong, Min Hao, Hui Gu, Bo Li This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8467036/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 13 You are reading this latest preprint version Abstract Objective To investigate the etiology and diagnostic approach of pancytopenia in children, with emphasis on uncommon nutritional causes, particularly in individuals with intellectual disability, whose dietary behaviors may predispose them to deficiency. The goal is to reduce misdiagnosis and therapeutic delays in clinical practice. Methods We retrospectively analyzed the clinical features, laboratory results, bone marrow findings, treatment, and outcomes of a child with trisomy 21 presenting with profound pancytopenia at Zaozhuang Municipal Hospital in November 2023, supplemented by a review of the literature. Results The patient exhibited severe pancytopenia at admission with WBC = 1.77×10⁹/L, RBC = 0.47×10¹²/L, hemoglobin = 21 g/L, and platelets = 5×10⁹/L. Bone marrow morphology, immunophenotyping, and serum folate/vitamin B12 assays confirmed megaloblastic anemia. Following folate and vitamin B12 replacement therapy, hematologic parameters progressively normalized. Conclusion The child was diagnosed with severe megaloblastic anemia (MA). MA typically causes macrocytic anemia and may lead to pancytopenia, although the case of profound pancytopenia with such severity is rare in the pediatric population in China. In cases with extremely low blood counts, differentiation from leukemia, myelodysplastic syndromes, and aplastic anemia is critical. Bone marrow aspiration and biopsy remain essential. Vitamin B12 deficiency in this case resulted in neuropsychiatric symptoms, including seizures, which improved substantially after vitamin replacement. This case underscores the importance of evaluating nutritional status in children with developmental delay and restricted dietary patterns. Figures Figure 1 Figure 2 Introduction Down Syndrome (DS) is caused by chromosomal abnormalities and is one of the most common chromosomal syndromes. Approximately 95% of patients exhibit complete trisomy 21 (47, XX/XY, + 21). The incidence among live births is approximately 1:600-1:1000. Clinical features include intellectual disability, characteristic facies, growth retardation, and frequent congenital malformations (e.g., congenital heart disease, gastrointestinal anomalies).¹ Due to trisomy 21, genes associated with leukemogenesis are overexpressed, impairing normal hematopoietic development and markedly increasing leukemia risk.² − ³ Literature reports suggest that children with DS have a 500-fold increased risk of acute megakaryoblastic leukemia (AMKL) and a 20-fold increased risk of acute lymphoblastic leukemia (ALL).⁴ − ⁵ In this patient, the sudden onset of profound pancytopenia raised strong suspicion for hematologic malignancy. This case explores the underlying cause and clinical reasoning. Clinical Data Present medical history : The patient was an 8-year-old boy who developed fever 3 days prior to admission, with a peak temperature of 38°C. He intermittently complained of headache and exhibited mild limb tremors. His family administered over-the-counter medications, including a pediatric acetaminophen-chlorpheniramine preparation, but the fever recurred. Approximately three hours before hospital admission, he experienced a generalized convulsive episode characterized by unresponsiveness, jaw clenching, and flaccid extremities. His temperature at that time was normal. He was taken to a local hospital where laboratory evaluation revealed severe pancytopenia: white blood cells (WBC) = 2.15×10⁹/L, red blood cells (RBC) = 0.52×10¹²/L, hemoglobin = 24 g/L, platelets = 4×10⁹/L, and an absolute neutrophil count of 0.2×10⁹/L. Given the severity of his condition, he was urgently transferred to our hospital for further evaluation and management. Past medical history Chromosomal analysis performed at 1 month of age confirmed trisomy 21 (47, XX/XY, + 21), establishing the diagnosis of Down Syndrome. He also had a history of congenital heart disease and underwent corrective cardiac surgery in May 2018 at Beijing Anzhen Hospital. Personal and family history The patient displayed significant delays in cognitive, language, and physical development compared with age-matched peers. He lived with both parents, who are schoolteachers with a moderate income level, and who provided full-time care. He had one older brother who was healthy. There was no reported family history of hematologic or genetic disorders. Physical Examination On admission, the patient’s vital signs were as follows: temperature 37°C, heart rate 127 beats per minute, blood pressure 107/70 mmHg, and body weight 21.5 kg. He exhibited characteristic phenotypic features of Down Syndrome, including global developmental delay and short, broad fingers with a single transverse palmar crease. His skin and mucous membranes appeared markedly pale, with scattered petechiae noted on the extremities. Pharyngeal congestion was present. Lung auscultation revealed no abnormal breath sounds. Cardiac examination identified a grade II-III systolic murmur. The abdominal examination was unremarkable, with no hepatosplenomegaly or tenderness. Neurological assessment showed fine tremors of both hands and feet, while the Babinski sign was negative. Laboratory Examinations Initial laboratory evaluation revealed profound pancytopenia, with a leukocyte count of 1.77×10⁹/L, erythrocyte count of 0.47×10¹²/L, hemoglobin level of 21 g/L, platelet count of 5×10⁹/L, and an absolute neutrophil count of 0.18×10⁹/L (Table 1 ). RBC indices demonstrated marked macrocytosis, with a mean corpuscular volume of 131.6 fL, accompanied by a significantly reduced reticulocyte count (6×10⁹/L). Serum lactate dehydrogenase was mildly elevated at 250 U/L (Table 1 ). Direct antiglobulin testing, anti-erythrocyte antibodies, and anti-human agglutinin assays were all negative. Liver and renal function tests were within normal limits. Evaluation of micronutrient status showed severe deficiencies, with folic acid at 0.79 ng/mL and vitamin B12 at 99.5 pg/mL, while ferritin was within the normal range at 268.2 ng/mL (Table 1 ). Cranial CT imaging demonstrated no abnormalities. Peripheral blood smear examination showed anisocytosis with some erythrocytes arranged in a partial “coin-stacking” pattern (Table 1 ). Table 1 Laboratory Examination Results Laboratory Exams Result Reference Range Leukocyte count 1.77×109/L 4.3–11.3 Erythrocyte count 0.47×1012/L 4.2–5.7 Hemoglobin 21g/L 118–156 Platelets count 5×109/L 167–453 Neutrophils absolute 0.18×109/L 1.6–7.8 Mean corpuscular volume 131.6fl 77–92 Reticulocytes absolute 6×109/L 24–84 Lactate dehydrogenase 250U/L 135–214 Anti-erythrocyte antibody Negative Anti-human agglutinin Negative Liver and kidney function Normal Folic acid 0.79ng/ml 3.89–26.8 Vitamin B12 99.5pg/ml 197–771 Ferritin 268.2ng/ml 22–322 Cranial CT Normal Peripheral blood smear Partly coin-shaped erythrocyte Bone Marrow Aspiration Evaluation Bone marrow aspiration resulted in a dry tap, and the limited smear obtained demonstrated markedly reduced nucleated cell content. Morphologic examination showed prominent megaloblastic changes across hematopoietic lineages. Granulocytic precursors appeared enlarged, with giant metamyelocytes observed. Erythroid precursors were increased in size with characteristic megaloblastic features, including nuclear-cytoplasmic asynchrony, Howell-Jolly (H-J) bodies, and occasional nuclear fragmentation. Megakaryocytes were notably absent in the sample(Figure 1 ). Flow Cytometry Analysis Flow cytometric immunophenotyping using CD45/SSC gating demonstrated no abnormalities in lymphocyte proportion or phenotype (Fig. 2 ). A small population of immature myeloid progenitor cells (P3), comprising 0.3% of nucleated cells, exhibited positivity for CD34, CD117, CD33, HLA-DR, CD13, and CD56, with weak CD45 expression and reduced CD38, consistent with mildly abnormal myeloid precursors rather than overt leukemic blasts. Granulocytes accounted for 51.4% of nucleated cells and showed increased cell size on scatter plots. Monocyte proportions and phenotypes remained within normal limits. Nucleated erythroid cells were markedly elevated at 32.8%, with enlarged cell size reflected by increased forward and side scatter signals (FSC/SSC). Gene sequencing was negative, providing no molecular evidence of clonal hematopoietic disease (Fig. 2 ). Medical Treatment As outlined in Table 2 , the patient received supportive transfusion therapy, including RBCs and platelets, from November 9 to November 12, 2023. Vitamin B12 replacement was initiated on November 12, beginning with intramuscular injections of 1 mg daily for 10 days, followed by weekly injections from November 22 to December 23, and then monthly injections for an additional two doses through January 2024. Concurrently, the patient was started on folic acid at 5 mg orally three times daily and vitamin C at 0.5 g three times daily. Potassium chloride sustained-release tablets (0.5 g orally three times daily) were administered to prevent hypokalemia. Nutritional counseling was provided, with emphasis on correcting unhealthy dietary habits by incorporating foods rich in folate and vitamin B12 to ensure balanced nutritional intake. Table 2 Treatment Timeline and Medications Date / Period Intervention Dosage & Frequency Purpose 2023.11.09–11.12 RBC & platelet transfusions — Correction of severe cytopenias 2023.11.12–11.22 Vitamin B12 IM 1 mg daily Rapid repletion for severe deficiency 2023.11.22–12.23 Vitamin B12 IM 1 mg weekly Continued replenishment 2023.12.23–2024.01.23 Vitamin B12 IM 1 mg monthly ×2 Maintenance 2023.11.12–2024.02 Folic acid PO 5 mg three times daily Correction of folate deficiency 2023.11.12–2024.02 Vitamin C PO 0.5 g three times daily Supportive therapy 2023.11.12–2024.02 KCl sustained-release PO 0.5 g three times daily Prevention of hypokalemia Ongoing Dietary modification — Nutritional rehabilitation 2023.11.09–11.12 RBC & platelet transfusions — Correction of severe cytopenias 2023.11.12–11.22 Vitamin B12 IM 1 mg daily Rapid repletion for severe deficiency 2023.11.22–12.23 Vitamin B12 IM 1 mg weekly Continued replenishment 2023.12.23–2024.01.23 Vitamin B12 IM 1 mg monthly ×2 Maintenance 2023.11.12–2024.02 Folic acid PO 5 mg three times daily Correction of folate deficiency 2023.11.12–2024.02 Vitamin C PO 0.5 g three times daily Supportive therapy 2023.11.12–2024.02 KCl sustained-release PO 0.5 g three times daily Prevention of hypokalemia Ongoing Dietary modification — Nutritional rehabilitation Follow-up Evaluation Following confirmation of the diagnosis, the patient was treated with intramuscular vitamin B12 and oral folic acid. As summarized in Table 3 , hematologic recovery began within four days of initiating therapy, with progressive improvement in all blood cell lineages. By approximately three weeks, the complete blood count had returned to near-normal levels. At the two-month follow-up visit, all hematologic parameters were fully normalized. Clinically, the patient showed marked improvement, with complete resolution of tremors and no recurrence of convulsive episodes. Table 3 Hematologic Parameters after Treatment Blood cell counts 4 days after initial treatment 7 days 10 days 14 days 21 days 2 months WBC (×10⁹/L) 1.94 8.35 6.98 11.71 5.64 7.47 RBC (×10¹²/L) 2.07 2.09 2.55 2.75 3.49 5.07 Hg (g/L) 69 70 84 95 114 155 PLT (×10⁹/L) 47 63 168 515 420 317 NE (×10⁹/L) 0.19 3.38 2.72 6.69 1.9 2.27 Ret % 0.4 4.2 7.4 8.5 5.7 1.5 Discussion Pancytopenia in children may arise from a wide spectrum of hematologic and systemic disorders, including leukemia, aplastic anemia (AA), myelodysplastic syndromes (MDS), hemophagocytic lymphohistiocytosis, immune-mediated hemolysis, paroxysmal nocturnal hemoglobinuria, megaloblastic anemia (MA), and various infectious diseases.⁶ In severe cases, both benign and malignant etiologies must be considered simultaneously.⁷ Given this patient’s profound pancytopenia at presentation, AA was initially suspected. AA typically presents with reductions in at least two hematopoietic lineages and hypocellular bone marrow (< 50% hematopoietic cellularity), and may also show increased mean corpuscular volume. Definitive diagnosis requires complete blood count, reticulocyte count, bone marrow aspiration, and biopsy.⁸ MDS may closely resemble MA in laboratory findings and bone marrow morphology, as both conditions can manifest macrocytic anemia and multilineage cytopenias.⁹ Consequently, MA is frequently misdiagnosed as MDS. Accurate differentiation relies on careful assessment of cellular morphology, hematologic indices, and genetic studies. The 2022 WHO classification emphasizes the diagnostic significance of MDS-associated mutations such as MDS-5q, MDS-SF3B1, and bi-allelic TP53 alterations.¹⁰ − ¹² In this patient, multiple bone marrow aspiration attempts yielded only scant material. The smear demonstrated markedly reduced nucleated cell numbers, which may have resulted from prolonged suppression of bone marrow proliferation or sampling limitations. This finding further underscores the necessity of performing bone marrow biopsy in children with severe cytopenias. Morphologic evaluation revealed classic megaloblastic changes in both granulocytic and erythroid lineages without features of dysplasia. Immunophenotyping identified only a minimal proportion (0.3%) of myeloid progenitors, and a large number of granulocytes and erythrocytes appeared enlarged, of which findings concordant with megaloblastic morphology rather than leukemia or MDS. Gene sequencing did not detect pathogenic variants, and cytogenetic studies demonstrated a normal karyotype. In addition, peripheral ferritin levels were normal, and lactate dehydrogenase was elevated, further supporting a diagnosis of MA. Subsequent testing confirmed significantly reduced serum folate and vitamin B12 levels, more supporting the diagnosis. MA is a macrocytic anemia resulting from folate or vitamin B12 deficiency, both of which are required for tetrahydrofolate production and DNA synthesis.¹³ Deficiency of either nutrient disrupts nuclear maturation, leading to ineffective erythropoiesis, macrocytosis (MCV > 100 fL), and shortened red blood cell lifespan. Studies report that RBC lifespan in MA is reduced by 30–50%, with contributions from both intravascular and extravascular hemolysis.¹⁴ , ¹⁵ Impaired DNA synthesis also affects granulocytic and megakaryocytic maturation, producing pancytopenia. Thus, MA can clinically mimic bone marrow failure syndromes, although pancytopenia is not unique to MA.¹⁶ Differentiating MA from other causes of marrow failure can be challenging without vitamin level assessment and marrow morphology. Folate and vitamin B12 are obtained primarily from animal organ meats, eggs, dairy products, red meat, fish, shellfish, and vegetables. Causes of deficiency include inadequate dietary intake (malnutrition, vegetarian diets, elderly, pregnancy, alcoholism), gastrointestinal surgery, malabsorption syndromes, atrophic gastritis, and use of certain medications such as antacids or metformin. In Western populations, vitamin B12 deficiency most commonly results from pernicious anemia caused by autoimmune destruction of gastric parietal cells or intrinsic factor impairment.¹⁷ , ¹⁸ Other causes include ileal disease and upper gastrointestinal surgery. Dietary deficiency alone is relatively uncommon except among strict vegetarians. In China, with improving socioeconomic conditions, isolated dietary vitamin B12 deficiency has become less frequent.¹⁹ The daily requirement for vitamin B12 is 2–3 µg, and body stores, mainly in the liver, are sufficient for 3–6 years without intake, whereas folate deficiency can develop within 6 months.²⁰ A detailed dietary history revealed that the patient consumed almost exclusively steamed buns since age 3, with minimal intake of meat, dairy products, vegetables, or other nutrient sources. There was no history of gastritis, gastrointestinal surgery, or medication use that could impair absorption. Thus, severe nutritional deficiency was identified as the clear etiology. Vitamin B12 deficiency often produces more profound anemia than folate deficiency, potentially due to interference with folate metabolism.²¹ , ²² Vitamin B12 also plays a critical role in myelin synthesis; its deficiency can cause central and peripheral demyelination, resulting in neurological manifestations such as flat affect, irritability, lethargy, developmental regression, tremors, ataxia, and seizures in severe cases.²³ Because children with trisomy 21 already exhibit baseline neurodevelopmental delay, distinguishing deficiency-related symptoms can be difficult. However, this patient’s seizure activity likely reflected severe B12 depletion rather than baseline Down syndrome–related neurological features. Treatment of MA consists of folic acid and vitamin B12 supplementation. Folic acid is typically administered orally at 1–5 mg daily. Vitamin B12 can be given orally or intramuscularly. Intramuscular cobalamin achieves rapid repletion, with approximately 10–15% of the injected dose retained, whereas oral absorption ranges from 0.5-4%.²⁴ Despite differing bioavailability, high-dose oral regimens are cost-effective and well tolerated, and have been shown to be equivalent to parenteral therapy in many cases.²⁵ For patients with malabsorption, feeding difficulties, or neurological involvement, guidelines recommend 1 mg intramuscularly daily for two weeks, followed by weekly injections for eight weeks. Once tissue stores are restored, a daily oral dose of ≥ 6 µg is sufficient due to efficient enterohepatic recycling.²⁰ , ²⁶ The patient received intramuscular vitamin B12 and oral folic acid according to recommended protocols. Hematologic recovery began within one week, and blood counts returned to near normal within three weeks. This treatment response is consistent with previously reported outcomes.²⁷ This case of severe pancytopenia highlights the importance of a comprehensive diagnostic approach in pediatric patients. To be mentioned,it needs to be further studied whether the extra chromosome participated and accelarated the synthetic impairment of DNA by more assemblings. Every human life should be respected, so we urge to concern about this vulnerable populaton and special attention should be given to dietary habits and nutritional status, as they are at increased risk of deficiencies that may mimic serious hematologic disorders. Early recognition of nutritional etiologies can prevent unnecessary invasive procedures and ensure timely, effective treatment. Declarations Clinical trial number Not applicable. Ethical approval and consent to participate: This is a case report and not a research report. Ethical approval was not required. All procedures performed were in accordance with the ethical standards of the institutional research committee. Consent for publication: Written informed consent was obtained from the parents of the patient for publication of this case report and any accompanying images. Competing interests: The authors declare no competing interests. Funding Not applicable. Author Contribution Y.Z., W.Y., D.G., H.G., M.H., and B.L. wrote the manuscript and prepared the figures and tables. Acknowledgements Not applicable. Data Availability All data and materials in this study are included in this published article. References Mazurek D, Wyka J. Down syndrome–genetic and nutritional aspects of accompanying disorders. Rocz Panstw Zakl Hig. 2015;66(3):189–94. Langebrake C. Klusmann JH,Wortmann K,etal.Concomitant aberrant overexpression of RUNX1 and NCAM in regenerating bone marrow of myeloid leukemia of Down's syndrome. Haematologica. 2006;91(11):1473–80. Brown AL, de Smith AJ, Gant VU, Yang W. etal.Inherited genetic susceptibility to acute lymphoblastic leukemia in Down syndrome[J].Blood. 2019;134(15):1227–37. Thakral B, Lin P. Acute myeloid leukemia with erythroid and megakaryocytic differentiation associated with Down syndrome.Blood. 2021;138(23):2446. Seewald L. Taub JW,Maloney KW,etal. Acute leukemias in children with Down syndrome. Mol Genet Metab. 2012;107(1–2):25–30. Pine M, Walter AW. Pancytopenia in hospitalized children: a five-year review. J Pediatr Hematol Oncol. 2010;32(5):e192–4. Steensma DP. Dysplasia has a differential diagnosis: distinguishing genuine myelodysplastic syndromes (MDS) from mimics, imitators, copycats and impostors. Curr Hematol Malig. 2012;7(4):310–20. Hartung HD, Olson TS, Bessler M. Acquired aplastic anemia in children. Pediatr Clin North Am. 2013;60(6):1311–36. Xu ZH. The bone morphological examination method for refractory anemia and megaloblasitc anemia[J]. World Clin Med 2016,10(6):239–40. Chisholm KM, Bohling SD. Childhood Myelodysplastic Syndrome. Clin Lab Med. 2023;43(4):639–55. Malcovati L, Stevenson K, Papaemmanuil, E,Neuberg, D,Bejar. R,Boultwood J,etal.SF3B1-mutant MDS as a distinct disease subtype:a proposal from the International Working Group for the Prognosis of. MDS Blood. 2020;136(2):157–70. Khoury JD, Solary E, Abla O, Akkari Y, Alaggio R, Apperley JF et al. The 5th edition of the World Health Organization Classification of Haematolymphoid Tumors:Myeloid and Histiocytic/Dendritic Neoplasms.Leukemia.2022;36(7):1703–1719. Tang L, Miao J, Wang J. Clinical characteristics of megaloblastic anemia with pancytopenia. Hematology. 2024;29(1):2420407. Aslinia F, Mazza JJ, Yale SH. Megaloblastic anemia and other causes of macrocytosis[J]. Clin Med Res. 2006;4(3):236–41. Zhang HD, Ma YJ, Liu QF, et al. Human erythrocyte lifespan measured by Levitt′s CO breath test with newly developed automatic instrument. J Breath Res. 2018;12(3):036003. Htut TW, Thein KZ, Oo TH. Pernicious anemia: Pathophysiology and diagnostic difficulties. J Evid Based Med. 2021;14(2):161–9. Esposito G, Dottori L, Pivetta G, Ligato I, Dilaghi E, Lahner E. etal. Pernicious Anemia: The Hematological Presentation of a Multifaceted Disorder Caused by Cobalamin Deficiency. Nutrients. 2022;14(8):1672. Neumann WL, Coss E, Rugge M, Genta RM. Autoimmune atrophic gastritis–pathogenesis, pathology and management. Nat Rev Gastroenterol Hepatol. 2013;10(9):529–41. Shen M, Luo X, Wu C, Wang J, Wang Z, Lei M. Meiqing Le Pernicious anemia is a common cause of cobalamin deficiency-caused megaloblastic anemia in Hainan. China Hematol. 2024;29(1):2399375. Green R, Allen LH, Bjørke-Monsen AL, Brito A, Guéant JL, Miller JW, Molloy AM, Nexo E, Stabler S, Toh BH, et al. Vitamin B12 deficiency. Nat Rev Dis Primers. 2017;3:17040. Green R. Vitamin B12 deficiency from the perspective of a practicing hematologist.Blood. 2017;129(19):2603–11. Steinberg SE, Fonda S, Campbell C, Hillman RS. Cellular abnormalities of folate deficiency. Br J Haematol. 1983;54(4):605–12. Stabler SP. Clinical practice. Vitamin B12 defi ciency. N Engl J Med. 2013;368(2):149–60. Infante M, Leoni M, Caprio M, Fabbri A. Long-term metformin therapy and vitamin B12 deficiency: An association to bear in mind. World J Diabetes 2021 July 15; 12(7): 916–31. Vidal-Alaball J, Butler CC, Cannings-John R et al. Oral vitamin B12 versus intramuscular vitamin B12 for vitamin B12 deficiency. Cochrane Database Syst Rev. 2005;(3):CD004655. Tandon R, Thacker J, Pandya U, Patel M, Tandon K. Parenteral vs Oral Vitamin B12 in Children With Nutritional Macrocytic Anemia: A Randomized Controlled Trial. Indian Pediatr. 2022;59(9):683–7. Epub 2022 May 31. Hillman RS, Adamson J, Burka E. Characteristics of vitamin B12 correction of the abnormal erythropoiesis of pernicious anemia. Blood. 1968;31(4):419–32. 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-8467036\",\"acceptedTermsAndConditions\":true,\"allowDirectSubmit\":false,\"archivedVersions\":[],\"articleType\":\"Case Report\",\"associatedPublications\":[],\"authors\":[{\"id\":579919715,\"identity\":\"7d64c820-9e1f-48f8-8364-c6d79c528e4d\",\"order_by\":0,\"name\":\"Ying Zheng\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"Zaozhuang Municipal Hospital\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Ying\",\"middleName\":\"\",\"lastName\":\"Zheng\",\"suffix\":\"\"},{\"id\":579919718,\"identity\":\"f5b4253d-21d2-45e2-9337-64879ab1e473\",\"order_by\":1,\"name\":\"Wenjun Yue\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"Zaozhuang Municipal Hospital\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Wenjun\",\"middleName\":\"\",\"lastName\":\"Yue\",\"suffix\":\"\"},{\"id\":579919721,\"identity\":\"6c7e901d-a44b-487c-817d-a9d558de0eee\",\"order_by\":2,\"name\":\"Dehong Gong\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"Zaozhuang Municipal Hospital\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Dehong\",\"middleName\":\"\",\"lastName\":\"Gong\",\"suffix\":\"\"},{\"id\":579919726,\"identity\":\"65bcc8e8-58da-4486-9bbf-a55e48d99503\",\"order_by\":3,\"name\":\"Min Hao\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"Zaozhuang Municipal Hospital\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Min\",\"middleName\":\"\",\"lastName\":\"Hao\",\"suffix\":\"\"},{\"id\":579919727,\"identity\":\"fc93a00b-377c-49d8-adb0-427d6e0b5969\",\"order_by\":4,\"name\":\"Hui Gu\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"Zaozhuang Shizhong District People's Hospital\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Hui\",\"middleName\":\"\",\"lastName\":\"Gu\",\"suffix\":\"\"},{\"id\":579919732,\"identity\":\"e9c2850a-e7d5-471f-9940-efd33281487c\",\"order_by\":5,\"name\":\"Bo Li\",\"email\":\"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAy0lEQVRIiWNgGAWjYBACPmYeBoaHDTY8bOzNBw58qCBCCxtIS2JDmhw/z7HEgzPOEKOFAazlsLHkDB/jw7wtxGhh5z34IHEHc+KGGzwfDvA2MMjzix0g5DC+ZIPEM2yJG273bjgguYPBcObsBIJ+MZNIbONJ3HDn7IYDhmcYEgxuE6dFAuiwnAcHEtuI12IA9H4Ow4GDxGkB+yUBFMgGBxvOSBD2Cz//2YMPPu74D4rKx5//VNjI80sT0IIOJEhTPgpGwSgYBaMAOwAA8GhHSnUX2coAAAAASUVORK5CYII=\",\"orcid\":\"\",\"institution\":\"Zaozhuang Municipal Hospital\",\"correspondingAuthor\":true,\"prefix\":\"\",\"firstName\":\"Bo\",\"middleName\":\"\",\"lastName\":\"Li\",\"suffix\":\"\"}],\"badges\":[],\"createdAt\":\"2025-12-28 17:08:15\",\"currentVersionCode\":1,\"declarations\":\"\",\"doi\":\"10.21203/rs.3.rs-8467036/v1\",\"doiUrl\":\"https://doi.org/10.21203/rs.3.rs-8467036/v1\",\"draftVersion\":[],\"editorialEvents\":[],\"editorialNote\":\"\",\"failedWorkflow\":false,\"files\":[{\"id\":101269133,\"identity\":\"413f698e-1192-4129-9c5d-376f4b4fc610\",\"added_by\":\"auto\",\"created_at\":\"2026-01-28 01:28:21\",\"extension\":\"jpg\",\"order_by\":1,\"title\":\"Figure 1\",\"display\":\"\",\"copyAsset\":false,\"role\":\"figure\",\"size\":159926,\"visible\":true,\"origin\":\"\",\"legend\":\"\\u003cp\\u003e\\u003cstrong\\u003eMorphology of bone marrow cells. \\u003c/strong\\u003eImaged showed few nucleated cells, nuclear-cytoplasmic desynchrony, nuclear irregularity, enlarged granulocytes including giant band forms, macrocytic erythrocytes and mature red blood cells were commonly seen, with H-J bodies, nuclear fragmentation and basophilic stippling.\\u003c/p\\u003e\",\"description\":\"\",\"filename\":\"1.jpg\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-8467036/v1/e7e68bacaab12acb235c1153.jpg\"},{\"id\":101296860,\"identity\":\"33d24756-bc22-428f-82e0-cb96c1502a80\",\"added_by\":\"auto\",\"created_at\":\"2026-01-28 09:22:08\",\"extension\":\"jpg\",\"order_by\":2,\"title\":\"Figure 2\",\"display\":\"\",\"copyAsset\":false,\"role\":\"figure\",\"size\":95683,\"visible\":true,\"origin\":\"\",\"legend\":\"\\u003cp\\u003e\\u003cstrong\\u003eFlow cytometric immunophenotyping of bone marrow cells. \\u003c/strong\\u003eFlow cytometry using CD45/SSC gating showed normal lymphocyte proportions and phenotypes. A small population of myeloid progenitor cells (0.3%) expressed CD34, CD117, CD33, HLA-DR, CD13, and CD56 with weak CD45 and reduced CD38 expression, indicating mildly abnormal myeloid precursors. Granulocytes comprised 51.4% of cells and appeared enlarged. Monocytes were normal in proportion and phenotype. Nucleated erythroid cells were increased (32.8%) with elevated FSC/SSC signals.\\u003c/p\\u003e\",\"description\":\"\",\"filename\":\"2.jpg\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-8467036/v1/5cdffcd9aa59edb28540dc48.jpg\"},{\"id\":101299017,\"identity\":\"7e2bf988-72f0-4cdb-bfb6-1b3eca71f0f0\",\"added_by\":\"auto\",\"created_at\":\"2026-01-28 09:39:09\",\"extension\":\"pdf\",\"order_by\":0,\"title\":\"\",\"display\":\"\",\"copyAsset\":false,\"role\":\"manuscript-pdf\",\"size\":919957,\"visible\":true,\"origin\":\"\",\"legend\":\"\",\"description\":\"\",\"filename\":\"manuscript.pdf\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-8467036/v1/7378afa3-02f5-4aea-a3b5-f3077de9b405.pdf\"}],\"financialInterests\":\"No competing interests reported.\",\"formattedTitle\":\"\\u003cp\\u003eA Rare Case of Down Syndrome with Severe Pancytopenia: Clinical Analysis and Literature Review\\u003c/p\\u003e\",\"fulltext\":[{\"header\":\"Introduction\",\"content\":\"\\u003cp\\u003eDown Syndrome (DS) is caused by chromosomal abnormalities and is one of the most common chromosomal syndromes. Approximately 95% of patients exhibit complete trisomy 21 (47, XX/XY, + 21). The incidence among live births is approximately 1:600-1:1000. Clinical features include intellectual disability, characteristic facies, growth retardation, and frequent congenital malformations (e.g., congenital heart disease, gastrointestinal anomalies).¹ Due to trisomy 21, genes associated with leukemogenesis are overexpressed, impairing normal hematopoietic development and markedly increasing leukemia risk.²\\u003csup\\u003e−\\u003c/sup\\u003e³ Literature reports suggest that children with DS have a 500-fold increased risk of acute megakaryoblastic leukemia (AMKL) and a 20-fold increased risk of acute lymphoblastic leukemia (ALL).⁴\\u003csup\\u003e−\\u003c/sup\\u003e⁵ In this patient, the sudden onset of profound pancytopenia raised strong suspicion for hematologic malignancy. This case explores the underlying cause and clinical reasoning.\\u003c/p\\u003e\"},{\"header\":\"Clinical Data\",\"content\":\"\\u003cp\\u003e \\u003cb\\u003ePresent medical history\\u003c/b\\u003e: The patient was an 8-year-old boy who developed fever 3 days prior to admission, with a peak temperature of 38°C. He intermittently complained of headache and exhibited mild limb tremors. His family administered over-the-counter medications, including a pediatric acetaminophen-chlorpheniramine preparation, but the fever recurred. Approximately three hours before hospital admission, he experienced a generalized convulsive episode characterized by unresponsiveness, jaw clenching, and flaccid extremities. His temperature at that time was normal. He was taken to a local hospital where laboratory evaluation revealed severe pancytopenia: white blood cells (WBC) = 2.15×10⁹/L, red blood cells (RBC) = 0.52×10¹²/L, hemoglobin = 24 g/L, platelets = 4×10⁹/L, and an absolute neutrophil count of 0.2×10⁹/L. Given the severity of his condition, he was urgently transferred to our hospital for further evaluation and management.\\u003c/p\\u003e\\u003cp\\u003e \\u003cstrong\\u003ePast medical history\\u003c/strong\\u003e \\u003c/p\\u003e\\u003cp\\u003eChromosomal analysis performed at 1 month of age confirmed trisomy 21 (47, XX/XY, + 21), establishing the diagnosis of Down Syndrome. He also had a history of congenital heart disease and underwent corrective cardiac surgery in May 2018 at Beijing Anzhen Hospital.\\u003c/p\\u003e\\u003cp\\u003e \\u003cstrong\\u003ePersonal and family history\\u003c/strong\\u003e \\u003c/p\\u003e\\u003cp\\u003eThe patient displayed significant delays in cognitive, language, and physical development compared with age-matched peers. He lived with both parents, who are schoolteachers with a moderate income level, and who provided full-time care. He had one older brother who was healthy. There was no reported family history of hematologic or genetic disorders.\\u003c/p\\u003e\\u003ch2\\u003ePhysical Examination\\u003c/h2\\u003e\\u003cp\\u003eOn admission, the patient’s vital signs were as follows: temperature 37°C, heart rate 127 beats per minute, blood pressure 107/70 mmHg, and body weight 21.5 kg. He exhibited characteristic phenotypic features of Down Syndrome, including global developmental delay and short, broad fingers with a single transverse palmar crease. His skin and mucous membranes appeared markedly pale, with scattered petechiae noted on the extremities. Pharyngeal congestion was present. Lung auscultation revealed no abnormal breath sounds. Cardiac examination identified a grade II-III systolic murmur. The abdominal examination was unremarkable, with no hepatosplenomegaly or tenderness. Neurological assessment showed fine tremors of both hands and feet, while the Babinski sign was negative.\\u003c/p\\u003e\\u003ch3\\u003eLaboratory Examinations\\u003c/h3\\u003e\\u003cp\\u003eInitial laboratory evaluation revealed profound pancytopenia, with a leukocyte count of 1.77×10⁹/L, erythrocyte count of 0.47×10¹²/L, hemoglobin level of 21 g/L, platelet count of 5×10⁹/L, and an absolute neutrophil count of 0.18×10⁹/L (Table\\u0026nbsp;\\u003cspan refid=\\\"Tab1\\\" class=\\\"InternalRef\\\"\\u003e1\\u003c/span\\u003e). RBC indices demonstrated marked macrocytosis, with a mean corpuscular volume of 131.6 fL, accompanied by a significantly reduced reticulocyte count (6×10⁹/L). Serum lactate dehydrogenase was mildly elevated at 250 U/L (Table\\u0026nbsp;\\u003cspan refid=\\\"Tab1\\\" class=\\\"InternalRef\\\"\\u003e1\\u003c/span\\u003e). Direct antiglobulin testing, anti-erythrocyte antibodies, and anti-human agglutinin assays were all negative. Liver and renal function tests were within normal limits. Evaluation of micronutrient status showed severe deficiencies, with folic acid at 0.79 ng/mL and vitamin B12 at 99.5 pg/mL, while ferritin was within the normal range at 268.2 ng/mL (Table\\u0026nbsp;\\u003cspan refid=\\\"Tab1\\\" class=\\\"InternalRef\\\"\\u003e1\\u003c/span\\u003e). Cranial CT imaging demonstrated no abnormalities. Peripheral blood smear examination showed anisocytosis with some erythrocytes arranged in a partial “coin-stacking” pattern (Table\\u0026nbsp;\\u003cspan refid=\\\"Tab1\\\" class=\\\"InternalRef\\\"\\u003e1\\u003c/span\\u003e).\\u003c/p\\u003e\\u003cdiv class=\\\"gridtable\\\"\\u003e\\u003cdiv align=\\\"left\\\" class=\\\"colspec\\\" colname=\\\"c1\\\" colnum=\\\"1\\\"\\u003e\\u003c/div\\u003e\\u003cdiv align=\\\"left\\\" class=\\\"colspec\\\" colname=\\\"c2\\\" colnum=\\\"2\\\"\\u003e\\u003c/div\\u003e\\u003cdiv align=\\\"left\\\" class=\\\"colspec\\\" colname=\\\"c3\\\" colnum=\\\"3\\\"\\u003e\\u003c/div\\u003e\\u003ctable float=\\\"Yes\\\" id=\\\"Tab1\\\" border=\\\"1\\\"\\u003e\\u003ccaption language=\\\"En\\\"\\u003e \\u003cdiv class=\\\"CaptionNumber\\\"\\u003eTable 1\\u003c/div\\u003e \\u003cdiv class=\\\"CaptionContent\\\"\\u003e \\u003cp\\u003eLaboratory Examination Results\\u003c/p\\u003e \\u003c/div\\u003e \\u003c/caption\\u003e\\u003ccolgroup cols=\\\"3\\\"\\u003e\\u003c/colgroup\\u003e\\u003cthead\\u003e\\u003ctr\\u003e\\u003cth align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eLaboratory Exams\\u003c/p\\u003e \\u003c/th\\u003e\\u003cth align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003eResult\\u003c/p\\u003e \\u003c/th\\u003e\\u003cth align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003eReference Range\\u003c/p\\u003e \\u003c/th\\u003e\\u003c/tr\\u003e\\u003c/thead\\u003e\\u003ctbody\\u003e\\u003ctr\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eLeukocyte count\\u003c/p\\u003e \\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e1.77×109/L\\u003c/p\\u003e \\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e4.3–11.3\\u003c/p\\u003e \\u003c/td\\u003e\\u003c/tr\\u003e\\u003ctr\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eErythrocyte count\\u003c/p\\u003e \\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e0.47×1012/L\\u003c/p\\u003e \\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e4.2–5.7\\u003c/p\\u003e \\u003c/td\\u003e\\u003c/tr\\u003e\\u003ctr\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eHemoglobin\\u003c/p\\u003e \\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e21g/L\\u003c/p\\u003e \\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e118–156\\u003c/p\\u003e \\u003c/td\\u003e\\u003c/tr\\u003e\\u003ctr\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003ePlatelets count\\u003c/p\\u003e \\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e5×109/L\\u003c/p\\u003e \\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e167–453\\u003c/p\\u003e \\u003c/td\\u003e\\u003c/tr\\u003e\\u003ctr\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eNeutrophils absolute\\u003c/p\\u003e \\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e0.18×109/L\\u003c/p\\u003e \\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e1.6–7.8\\u003c/p\\u003e \\u003c/td\\u003e\\u003c/tr\\u003e\\u003ctr\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eMean corpuscular volume\\u003c/p\\u003e \\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e131.6fl\\u003c/p\\u003e \\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e77–92\\u003c/p\\u003e \\u003c/td\\u003e\\u003c/tr\\u003e\\u003ctr\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eReticulocytes absolute\\u003c/p\\u003e \\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e6×109/L\\u003c/p\\u003e \\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e24–84\\u003c/p\\u003e \\u003c/td\\u003e\\u003c/tr\\u003e\\u003ctr\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eLactate dehydrogenase\\u003c/p\\u003e \\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e250U/L\\u003c/p\\u003e \\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e135–214\\u003c/p\\u003e \\u003c/td\\u003e\\u003c/tr\\u003e\\u003ctr\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eAnti-erythrocyte antibody\\u003c/p\\u003e \\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003eNegative\\u003c/p\\u003e \\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e\\u003c/tr\\u003e\\u003ctr\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eAnti-human agglutinin\\u003c/p\\u003e \\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003eNegative\\u003c/p\\u003e \\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e\\u003c/tr\\u003e\\u003ctr\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eLiver and kidney function\\u003c/p\\u003e \\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003eNormal\\u003c/p\\u003e \\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e\\u003c/tr\\u003e\\u003ctr\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eFolic acid\\u003c/p\\u003e \\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e0.79ng/ml\\u003c/p\\u003e \\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e3.89–26.8\\u003c/p\\u003e \\u003c/td\\u003e\\u003c/tr\\u003e\\u003ctr\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eVitamin B12\\u003c/p\\u003e \\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e99.5pg/ml\\u003c/p\\u003e \\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e197–771\\u003c/p\\u003e \\u003c/td\\u003e\\u003c/tr\\u003e\\u003ctr\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eFerritin\\u003c/p\\u003e \\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e268.2ng/ml\\u003c/p\\u003e \\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e22–322\\u003c/p\\u003e \\u003c/td\\u003e\\u003c/tr\\u003e\\u003ctr\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eCranial CT\\u003c/p\\u003e \\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003eNormal\\u003c/p\\u003e \\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e\\u003c/tr\\u003e\\u003ctr\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003ePeripheral blood smear\\u003c/p\\u003e \\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003ePartly coin-shaped erythrocyte\\u003c/p\\u003e \\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e\\u003c/tr\\u003e\\u003c/tbody\\u003e\\u003c/table\\u003e\\u003c/div\\u003e\\u003ch3\\u003eBone Marrow Aspiration Evaluation\\u003c/h3\\u003e\\u003cp\\u003eBone marrow aspiration resulted in a dry tap, and the limited smear obtained demonstrated markedly reduced nucleated cell content. Morphologic examination showed prominent megaloblastic changes across hematopoietic lineages. Granulocytic precursors appeared enlarged, with giant metamyelocytes observed. Erythroid precursors were increased in size with characteristic megaloblastic features, including nuclear-cytoplasmic asynchrony, Howell-Jolly (H-J) bodies, and occasional nuclear fragmentation. Megakaryocytes were notably absent in the sample(Figure \\u003cspan refid=\\\"Fig1\\\" class=\\\"InternalRef\\\"\\u003e1\\u003c/span\\u003e).\\u003c/p\\u003e\\u003ch3\\u003eFlow Cytometry Analysis\\u003c/h3\\u003e\\u003cp\\u003eFlow cytometric immunophenotyping using CD45/SSC gating demonstrated no abnormalities in lymphocyte proportion or phenotype (Fig.\\u0026nbsp;\\u003cspan refid=\\\"Fig2\\\" class=\\\"InternalRef\\\"\\u003e2\\u003c/span\\u003e). A small population of immature myeloid progenitor cells (P3), comprising 0.3% of nucleated cells, exhibited positivity for CD34, CD117, CD33, HLA-DR, CD13, and CD56, with weak CD45 expression and reduced CD38, consistent with mildly abnormal myeloid precursors rather than overt leukemic blasts. Granulocytes accounted for 51.4% of nucleated cells and showed increased cell size on scatter plots. Monocyte proportions and phenotypes remained within normal limits. Nucleated erythroid cells were markedly elevated at 32.8%, with enlarged cell size reflected by increased forward and side scatter signals (FSC/SSC). Gene sequencing was negative, providing no molecular evidence of clonal hematopoietic disease (Fig.\\u0026nbsp;\\u003cspan refid=\\\"Fig2\\\" class=\\\"InternalRef\\\"\\u003e2\\u003c/span\\u003e).\\u003c/p\\u003e\\u003ch3\\u003eMedical Treatment\\u003c/h3\\u003e\\u003cp\\u003eAs outlined in Table\\u0026nbsp;\\u003cspan refid=\\\"Tab2\\\" class=\\\"InternalRef\\\"\\u003e2\\u003c/span\\u003e, the patient received supportive transfusion therapy, including RBCs and platelets, from November 9 to November 12, 2023. Vitamin B12 replacement was initiated on November 12, beginning with intramuscular injections of 1 mg daily for 10 days, followed by weekly injections from November 22 to December 23, and then monthly injections for an additional two doses through January 2024. Concurrently, the patient was started on folic acid at 5 mg orally three times daily and vitamin C at 0.5 g three times daily. Potassium chloride sustained-release tablets (0.5 g orally three times daily) were administered to prevent hypokalemia. Nutritional counseling was provided, with emphasis on correcting unhealthy dietary habits by incorporating foods rich in folate and vitamin B12 to ensure balanced nutritional intake.\\u003c/p\\u003e\\u003cdiv class=\\\"gridtable\\\"\\u003e\\u003cdiv align=\\\"left\\\" class=\\\"colspec\\\" colname=\\\"c1\\\" colnum=\\\"1\\\"\\u003e\\u003c/div\\u003e\\u003cdiv align=\\\"left\\\" class=\\\"colspec\\\" colname=\\\"c2\\\" colnum=\\\"2\\\"\\u003e\\u003c/div\\u003e\\u003cdiv align=\\\"left\\\" class=\\\"colspec\\\" colname=\\\"c3\\\" colnum=\\\"3\\\"\\u003e\\u003c/div\\u003e\\u003cdiv align=\\\"left\\\" class=\\\"colspec\\\" colname=\\\"c4\\\" colnum=\\\"4\\\"\\u003e\\u003c/div\\u003e\\u003ctable float=\\\"Yes\\\" id=\\\"Tab2\\\" border=\\\"1\\\"\\u003e\\u003ccaption language=\\\"En\\\"\\u003e \\u003cdiv class=\\\"CaptionNumber\\\"\\u003eTable 2\\u003c/div\\u003e \\u003cdiv class=\\\"CaptionContent\\\"\\u003e \\u003cp\\u003eTreatment Timeline and Medications\\u003c/p\\u003e \\u003c/div\\u003e \\u003c/caption\\u003e\\u003ccolgroup cols=\\\"4\\\"\\u003e\\u003c/colgroup\\u003e\\u003cthead\\u003e\\u003ctr\\u003e\\u003cth align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eDate / Period\\u003c/p\\u003e \\u003c/th\\u003e\\u003cth align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003eIntervention\\u003c/p\\u003e \\u003c/th\\u003e\\u003cth align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003eDosage \\u0026amp; Frequency\\u003c/p\\u003e \\u003c/th\\u003e\\u003cth align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003ePurpose\\u003c/p\\u003e \\u003c/th\\u003e\\u003c/tr\\u003e\\u003c/thead\\u003e\\u003ctbody\\u003e\\u003ctr\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003e2023.11.09–11.12\\u003c/p\\u003e \\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003eRBC \\u0026amp; platelet transfusions\\u003c/p\\u003e \\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e—\\u003c/p\\u003e \\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003eCorrection of severe cytopenias\\u003c/p\\u003e \\u003c/td\\u003e\\u003c/tr\\u003e\\u003ctr\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003e2023.11.12–11.22\\u003c/p\\u003e \\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003eVitamin B12 IM\\u003c/p\\u003e \\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e1 mg daily\\u003c/p\\u003e \\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003eRapid repletion for severe deficiency\\u003c/p\\u003e \\u003c/td\\u003e\\u003c/tr\\u003e\\u003ctr\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003e2023.11.22–12.23\\u003c/p\\u003e \\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003eVitamin B12 IM\\u003c/p\\u003e \\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e1 mg weekly\\u003c/p\\u003e \\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003eContinued replenishment\\u003c/p\\u003e \\u003c/td\\u003e\\u003c/tr\\u003e\\u003ctr\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003e2023.12.23–2024.01.23\\u003c/p\\u003e \\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003eVitamin B12 IM\\u003c/p\\u003e \\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e1 mg monthly ×2\\u003c/p\\u003e \\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003eMaintenance\\u003c/p\\u003e \\u003c/td\\u003e\\u003c/tr\\u003e\\u003ctr\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003e2023.11.12–2024.02\\u003c/p\\u003e \\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003eFolic acid PO\\u003c/p\\u003e \\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e5 mg three times daily\\u003c/p\\u003e \\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003eCorrection of folate deficiency\\u003c/p\\u003e \\u003c/td\\u003e\\u003c/tr\\u003e\\u003ctr\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003e2023.11.12–2024.02\\u003c/p\\u003e \\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003eVitamin C PO\\u003c/p\\u003e \\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e0.5 g three times daily\\u003c/p\\u003e \\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003eSupportive therapy\\u003c/p\\u003e \\u003c/td\\u003e\\u003c/tr\\u003e\\u003ctr\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003e2023.11.12–2024.02\\u003c/p\\u003e \\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003eKCl sustained-release PO\\u003c/p\\u003e \\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e0.5 g three times daily\\u003c/p\\u003e \\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003ePrevention of hypokalemia\\u003c/p\\u003e \\u003c/td\\u003e\\u003c/tr\\u003e\\u003ctr\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eOngoing\\u003c/p\\u003e \\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003eDietary modification\\u003c/p\\u003e \\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e—\\u003c/p\\u003e \\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003eNutritional rehabilitation\\u003c/p\\u003e \\u003c/td\\u003e\\u003c/tr\\u003e\\u003ctr\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003e2023.11.09–11.12\\u003c/p\\u003e \\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003eRBC \\u0026amp; platelet transfusions\\u003c/p\\u003e \\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e—\\u003c/p\\u003e \\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003eCorrection of severe cytopenias\\u003c/p\\u003e \\u003c/td\\u003e\\u003c/tr\\u003e\\u003ctr\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003e2023.11.12–11.22\\u003c/p\\u003e \\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003eVitamin B12 IM\\u003c/p\\u003e \\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e1 mg daily\\u003c/p\\u003e \\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003eRapid repletion for severe deficiency\\u003c/p\\u003e \\u003c/td\\u003e\\u003c/tr\\u003e\\u003ctr\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003e2023.11.22–12.23\\u003c/p\\u003e \\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003eVitamin B12 IM\\u003c/p\\u003e \\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e1 mg weekly\\u003c/p\\u003e \\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003eContinued replenishment\\u003c/p\\u003e \\u003c/td\\u003e\\u003c/tr\\u003e\\u003ctr\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003e2023.12.23–2024.01.23\\u003c/p\\u003e \\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003eVitamin B12 IM\\u003c/p\\u003e \\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e1 mg monthly ×2\\u003c/p\\u003e \\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003eMaintenance\\u003c/p\\u003e \\u003c/td\\u003e\\u003c/tr\\u003e\\u003ctr\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003e2023.11.12–2024.02\\u003c/p\\u003e \\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003eFolic acid PO\\u003c/p\\u003e \\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e5 mg three times daily\\u003c/p\\u003e \\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003eCorrection of folate deficiency\\u003c/p\\u003e \\u003c/td\\u003e\\u003c/tr\\u003e\\u003ctr\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003e2023.11.12–2024.02\\u003c/p\\u003e \\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003eVitamin C PO\\u003c/p\\u003e \\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e0.5 g three times daily\\u003c/p\\u003e \\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003eSupportive therapy\\u003c/p\\u003e \\u003c/td\\u003e\\u003c/tr\\u003e\\u003ctr\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003e2023.11.12–2024.02\\u003c/p\\u003e \\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003eKCl sustained-release PO\\u003c/p\\u003e \\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e0.5 g three times daily\\u003c/p\\u003e \\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003ePrevention of hypokalemia\\u003c/p\\u003e \\u003c/td\\u003e\\u003c/tr\\u003e\\u003ctr\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eOngoing\\u003c/p\\u003e \\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003eDietary modification\\u003c/p\\u003e \\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e—\\u003c/p\\u003e \\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003eNutritional rehabilitation\\u003c/p\\u003e \\u003c/td\\u003e\\u003c/tr\\u003e\\u003c/tbody\\u003e\\u003c/table\\u003e\\u003c/div\\u003e\\u003ch2\\u003eFollow-up Evaluation\\u003c/h2\\u003e\\u003cp\\u003eFollowing confirmation of the diagnosis, the patient was treated with intramuscular vitamin B12 and oral folic acid. As summarized in Table\\u0026nbsp;\\u003cspan refid=\\\"Tab3\\\" class=\\\"InternalRef\\\"\\u003e3\\u003c/span\\u003e, hematologic recovery began within four days of initiating therapy, with progressive improvement in all blood cell lineages. By approximately three weeks, the complete blood count had returned to near-normal levels. At the two-month follow-up visit, all hematologic parameters were fully normalized. Clinically, the patient showed marked improvement, with complete resolution of tremors and no recurrence of convulsive episodes.\\u003c/p\\u003e\\u003cdiv class=\\\"gridtable\\\"\\u003e\\u003cdiv align=\\\"left\\\" class=\\\"colspec\\\" colname=\\\"c1\\\" colnum=\\\"1\\\"\\u003e\\u003c/div\\u003e\\u003cdiv align=\\\"left\\\" class=\\\"colspec\\\" colname=\\\"c2\\\" colnum=\\\"2\\\"\\u003e\\u003c/div\\u003e\\u003cdiv align=\\\"left\\\" class=\\\"colspec\\\" colname=\\\"c3\\\" colnum=\\\"3\\\"\\u003e\\u003c/div\\u003e\\u003cdiv align=\\\"left\\\" class=\\\"colspec\\\" colname=\\\"c4\\\" colnum=\\\"4\\\"\\u003e\\u003c/div\\u003e\\u003cdiv align=\\\"left\\\" class=\\\"colspec\\\" colname=\\\"c5\\\" colnum=\\\"5\\\"\\u003e\\u003c/div\\u003e\\u003cdiv align=\\\"left\\\" class=\\\"colspec\\\" colname=\\\"c6\\\" colnum=\\\"6\\\"\\u003e\\u003c/div\\u003e\\u003cdiv align=\\\"left\\\" class=\\\"colspec\\\" colname=\\\"c7\\\" colnum=\\\"7\\\"\\u003e\\u003c/div\\u003e\\u003ctable float=\\\"Yes\\\" id=\\\"Tab3\\\" border=\\\"1\\\"\\u003e\\u003ccaption language=\\\"En\\\"\\u003e \\u003cdiv class=\\\"CaptionNumber\\\"\\u003eTable 3\\u003c/div\\u003e \\u003cdiv class=\\\"CaptionContent\\\"\\u003e \\u003cp\\u003eHematologic Parameters after Treatment\\u003c/p\\u003e \\u003c/div\\u003e \\u003c/caption\\u003e\\u003ccolgroup cols=\\\"7\\\"\\u003e\\u003c/colgroup\\u003e\\u003cthead\\u003e\\u003ctr\\u003e\\u003cth align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eBlood cell counts\\u003c/p\\u003e \\u003c/th\\u003e\\u003cth align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e4 days after initial treatment\\u003c/p\\u003e \\u003c/th\\u003e\\u003cth align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e7 days\\u003c/p\\u003e \\u003c/th\\u003e\\u003cth align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e10 days\\u003c/p\\u003e \\u003c/th\\u003e\\u003cth align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e14 days\\u003c/p\\u003e \\u003c/th\\u003e\\u003cth align=\\\"left\\\" colname=\\\"c6\\\"\\u003e \\u003cp\\u003e21 days\\u003c/p\\u003e \\u003c/th\\u003e\\u003cth align=\\\"left\\\" colname=\\\"c7\\\"\\u003e \\u003cp\\u003e2 months\\u003c/p\\u003e \\u003c/th\\u003e\\u003c/tr\\u003e\\u003c/thead\\u003e\\u003ctbody\\u003e\\u003ctr\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eWBC (×10⁹/L)\\u003c/p\\u003e \\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e1.94\\u003c/p\\u003e \\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e8.35\\u003c/p\\u003e \\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e6.98\\u003c/p\\u003e \\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e11.71\\u003c/p\\u003e \\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c6\\\"\\u003e \\u003cp\\u003e5.64\\u003c/p\\u003e \\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c7\\\"\\u003e \\u003cp\\u003e7.47\\u003c/p\\u003e \\u003c/td\\u003e\\u003c/tr\\u003e\\u003ctr\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eRBC (×10¹²/L)\\u003c/p\\u003e \\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e2.07\\u003c/p\\u003e \\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e2.09\\u003c/p\\u003e \\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e2.55\\u003c/p\\u003e \\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e2.75\\u003c/p\\u003e \\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c6\\\"\\u003e \\u003cp\\u003e3.49\\u003c/p\\u003e \\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c7\\\"\\u003e \\u003cp\\u003e5.07\\u003c/p\\u003e \\u003c/td\\u003e\\u003c/tr\\u003e\\u003ctr\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eHg (g/L)\\u003c/p\\u003e \\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e69\\u003c/p\\u003e \\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e70\\u003c/p\\u003e \\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e84\\u003c/p\\u003e \\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e95\\u003c/p\\u003e \\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c6\\\"\\u003e \\u003cp\\u003e114\\u003c/p\\u003e \\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c7\\\"\\u003e \\u003cp\\u003e155\\u003c/p\\u003e \\u003c/td\\u003e\\u003c/tr\\u003e\\u003ctr\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003ePLT (×10⁹/L)\\u003c/p\\u003e \\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e47\\u003c/p\\u003e \\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e63\\u003c/p\\u003e \\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e168\\u003c/p\\u003e \\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e515\\u003c/p\\u003e \\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c6\\\"\\u003e \\u003cp\\u003e420\\u003c/p\\u003e \\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c7\\\"\\u003e \\u003cp\\u003e317\\u003c/p\\u003e \\u003c/td\\u003e\\u003c/tr\\u003e\\u003ctr\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eNE (×10⁹/L)\\u003c/p\\u003e \\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e0.19\\u003c/p\\u003e \\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e3.38\\u003c/p\\u003e \\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e2.72\\u003c/p\\u003e \\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e6.69\\u003c/p\\u003e \\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c6\\\"\\u003e \\u003cp\\u003e1.9\\u003c/p\\u003e \\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c7\\\"\\u003e \\u003cp\\u003e2.27\\u003c/p\\u003e \\u003c/td\\u003e\\u003c/tr\\u003e\\u003ctr\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eRet %\\u003c/p\\u003e \\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e0.4\\u003c/p\\u003e \\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e4.2\\u003c/p\\u003e \\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e7.4\\u003c/p\\u003e \\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e8.5\\u003c/p\\u003e \\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c6\\\"\\u003e \\u003cp\\u003e5.7\\u003c/p\\u003e \\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c7\\\"\\u003e \\u003cp\\u003e1.5\\u003c/p\\u003e \\u003c/td\\u003e\\u003c/tr\\u003e\\u003c/tbody\\u003e\\u003c/table\\u003e\\u003c/div\\u003e\"},{\"header\":\"Discussion\",\"content\":\"\\u003cp\\u003ePancytopenia in children may arise from a wide spectrum of hematologic and systemic disorders, including leukemia, aplastic anemia (AA), myelodysplastic syndromes (MDS), hemophagocytic lymphohistiocytosis, immune-mediated hemolysis, paroxysmal nocturnal hemoglobinuria, megaloblastic anemia (MA), and various infectious diseases.⁶ In severe cases, both benign and malignant etiologies must be considered simultaneously.⁷ Given this patient\\u0026rsquo;s profound pancytopenia at presentation, AA was initially suspected. AA typically presents with reductions in at least two hematopoietic lineages and hypocellular bone marrow (\\u0026lt;\\u0026thinsp;50% hematopoietic cellularity), and may also show increased mean corpuscular volume. Definitive diagnosis requires complete blood count, reticulocyte count, bone marrow aspiration, and biopsy.⁸ MDS may closely resemble MA in laboratory findings and bone marrow morphology, as both conditions can manifest macrocytic anemia and multilineage cytopenias.⁹ Consequently, MA is frequently misdiagnosed as MDS. Accurate differentiation relies on careful assessment of cellular morphology, hematologic indices, and genetic studies. The 2022 WHO classification emphasizes the diagnostic significance of MDS-associated mutations such as MDS-5q, MDS-SF3B1, and bi-allelic TP53 alterations.\\u0026sup1;⁰\\u003csup\\u003e\\u0026minus;\\u003c/sup\\u003e\\u0026sup1;\\u0026sup2;\\u003c/p\\u003e \\u003cp\\u003eIn this patient, multiple bone marrow aspiration attempts yielded only scant material. The smear demonstrated markedly reduced nucleated cell numbers, which may have resulted from prolonged suppression of bone marrow proliferation or sampling limitations. This finding further underscores the necessity of performing bone marrow biopsy in children with severe cytopenias. Morphologic evaluation revealed classic megaloblastic changes in both granulocytic and erythroid lineages without features of dysplasia. Immunophenotyping identified only a minimal proportion (0.3%) of myeloid progenitors, and a large number of granulocytes and erythrocytes appeared enlarged, of which findings concordant with megaloblastic morphology rather than leukemia or MDS. Gene sequencing did not detect pathogenic variants, and cytogenetic studies demonstrated a normal karyotype. In addition, peripheral ferritin levels were normal, and lactate dehydrogenase was elevated, further supporting a diagnosis of MA. Subsequent testing confirmed significantly reduced serum folate and vitamin B12 levels, more supporting the diagnosis.\\u003c/p\\u003e \\u003cp\\u003eMA is a macrocytic anemia resulting from folate or vitamin B12 deficiency, both of which are required for tetrahydrofolate production and DNA synthesis.\\u0026sup1;\\u0026sup3; Deficiency of either nutrient disrupts nuclear maturation, leading to ineffective erythropoiesis, macrocytosis (MCV\\u0026thinsp;\\u0026gt;\\u0026thinsp;100 fL), and shortened red blood cell lifespan. Studies report that RBC lifespan in MA is reduced by 30\\u0026ndash;50%, with contributions from both intravascular and extravascular hemolysis.\\u0026sup1;⁴\\u003csup\\u003e,\\u003c/sup\\u003e\\u0026sup1;⁵ Impaired DNA synthesis also affects granulocytic and megakaryocytic maturation, producing pancytopenia. Thus, MA can clinically mimic bone marrow failure syndromes, although pancytopenia is not unique to MA.\\u0026sup1;⁶ Differentiating MA from other causes of marrow failure can be challenging without vitamin level assessment and marrow morphology.\\u003c/p\\u003e \\u003cp\\u003eFolate and vitamin B12 are obtained primarily from animal organ meats, eggs, dairy products, red meat, fish, shellfish, and vegetables. Causes of deficiency include inadequate dietary intake (malnutrition, vegetarian diets, elderly, pregnancy, alcoholism), gastrointestinal surgery, malabsorption syndromes, atrophic gastritis, and use of certain medications such as antacids or metformin. In Western populations, vitamin B12 deficiency most commonly results from pernicious anemia caused by autoimmune destruction of gastric parietal cells or intrinsic factor impairment.\\u0026sup1;⁷\\u003csup\\u003e,\\u003c/sup\\u003e\\u0026sup1;⁸ Other causes include ileal disease and upper gastrointestinal surgery. Dietary deficiency alone is relatively uncommon except among strict vegetarians. In China, with improving socioeconomic conditions, isolated dietary vitamin B12 deficiency has become less frequent.\\u0026sup1;⁹ The daily requirement for vitamin B12 is 2\\u0026ndash;3 \\u0026micro;g, and body stores, mainly in the liver, are sufficient for 3\\u0026ndash;6 years without intake, whereas folate deficiency can develop within 6 months.\\u0026sup2;⁰\\u003c/p\\u003e \\u003cp\\u003eA detailed dietary history revealed that the patient consumed almost exclusively steamed buns since age 3, with minimal intake of meat, dairy products, vegetables, or other nutrient sources. There was no history of gastritis, gastrointestinal surgery, or medication use that could impair absorption. Thus, severe nutritional deficiency was identified as the clear etiology. Vitamin B12 deficiency often produces more profound anemia than folate deficiency, potentially due to interference with folate metabolism.\\u0026sup2;\\u0026sup1;\\u003csup\\u003e,\\u003c/sup\\u003e\\u0026sup2;\\u0026sup2; Vitamin B12 also plays a critical role in myelin synthesis; its deficiency can cause central and peripheral demyelination, resulting in neurological manifestations such as flat affect, irritability, lethargy, developmental regression, tremors, ataxia, and seizures in severe cases.\\u0026sup2;\\u0026sup3; Because children with trisomy 21 already exhibit baseline neurodevelopmental delay, distinguishing deficiency-related symptoms can be difficult. However, this patient\\u0026rsquo;s seizure activity likely reflected severe B12 depletion rather than baseline Down syndrome\\u0026ndash;related neurological features. Treatment of MA consists of folic acid and vitamin B12 supplementation. Folic acid is typically administered orally at 1\\u0026ndash;5 mg daily. Vitamin B12 can be given orally or intramuscularly. Intramuscular cobalamin achieves rapid repletion, with approximately 10\\u0026ndash;15% of the injected dose retained, whereas oral absorption ranges from 0.5-4%.\\u0026sup2;⁴ Despite differing bioavailability, high-dose oral regimens are cost-effective and well tolerated, and have been shown to be equivalent to parenteral therapy in many cases.\\u0026sup2;⁵ For patients with malabsorption, feeding difficulties, or neurological involvement, guidelines recommend 1 mg intramuscularly daily for two weeks, followed by weekly injections for eight weeks. Once tissue stores are restored, a daily oral dose of \\u0026ge;\\u0026thinsp;6 \\u0026micro;g is sufficient due to efficient enterohepatic recycling.\\u0026sup2;⁰\\u003csup\\u003e,\\u003c/sup\\u003e\\u0026sup2;⁶ The patient received intramuscular vitamin B12 and oral folic acid according to recommended protocols. Hematologic recovery began within one week, and blood counts returned to near normal within three weeks. This treatment response is consistent with previously reported outcomes.\\u0026sup2;⁷\\u003c/p\\u003e \\u003cp\\u003eThis case of severe pancytopenia highlights the importance of a comprehensive diagnostic approach in pediatric patients. To be mentioned,it needs to be further studied whether the extra chromosome participated and accelarated the synthetic impairment of DNA by more assemblings. Every human life should be respected, so we urge to concern about this vulnerable populaton and special attention should be given to dietary habits and nutritional status, as they are at increased risk of deficiencies that may mimic serious hematologic disorders. Early recognition of nutritional etiologies can prevent unnecessary invasive procedures and ensure timely, effective treatment.\\u003c/p\\u003e\"},{\"header\":\"Declarations\",\"content\":\"\\u003cp\\u003e \\u003cstrong\\u003eClinical trial number\\u003c/strong\\u003e \\u003cp\\u003eNot applicable.\\u003c/p\\u003e \\u003c/p\\u003e \\u003cp\\u003e \\u003cstrong\\u003eEthical approval and consent to participate:\\u003c/strong\\u003e \\u003cp\\u003eThis is a case report and not a research report. Ethical approval was not required. All procedures performed were in accordance with the ethical standards of the institutional research committee.\\u003c/p\\u003e \\u003c/p\\u003e \\u003cp\\u003e \\u003cstrong\\u003eConsent for publication:\\u003c/strong\\u003e \\u003cp\\u003e Written informed consent was obtained from the parents of the patient for publication of this case report and any accompanying images.\\u003c/p\\u003e \\u003c/p\\u003e \\u003cp\\u003e \\u003cstrong\\u003eCompeting interests:\\u003c/strong\\u003e \\u003cp\\u003eThe authors declare no competing interests.\\u003c/p\\u003e \\u003c/p\\u003e\\u003ch2\\u003eFunding\\u003c/h2\\u003e \\u003cp\\u003eNot applicable.\\u003c/p\\u003e\\u003ch2\\u003eAuthor Contribution\\u003c/h2\\u003e\\u003cp\\u003eY.Z., W.Y., D.G., H.G., M.H., and B.L. wrote the manuscript and prepared the figures and tables.\\u003c/p\\u003e\\u003ch2\\u003eAcknowledgements\\u003c/h2\\u003e \\u003cp\\u003eNot applicable.\\u003c/p\\u003e\\u003ch2\\u003eData Availability\\u003c/h2\\u003e\\u003cp\\u003eAll data and materials in this study are included in this published article.\\u003c/p\\u003e\"},{\"header\":\"References\",\"content\":\"\\u003col\\u003e\\u003cli\\u003e\\u003cspan\\u003eMazurek D, Wyka J. Down syndrome\\u0026ndash;genetic and nutritional aspects of accompanying disorders. Rocz Panstw Zakl Hig. 2015;66(3):189\\u0026ndash;94.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eLangebrake C. Klusmann JH,Wortmann K,etal.Concomitant aberrant overexpression of RUNX1 and NCAM in regenerating bone marrow of myeloid leukemia of Down's syndrome. Haematologica. 2006;91(11):1473\\u0026ndash;80.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eBrown AL, de Smith AJ, Gant VU, Yang W. etal.Inherited genetic susceptibility to acute lymphoblastic leukemia in Down syndrome[J].Blood. 2019;134(15):1227\\u0026ndash;37.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eThakral B, Lin P. Acute myeloid leukemia with erythroid and megakaryocytic differentiation associated with Down syndrome.Blood. 2021;138(23):2446.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eSeewald L. Taub JW,Maloney KW,etal. Acute leukemias in children with Down syndrome. Mol Genet Metab. 2012;107(1\\u0026ndash;2):25\\u0026ndash;30.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003ePine M, Walter AW. Pancytopenia in hospitalized children: a five-year review. J Pediatr Hematol Oncol. 2010;32(5):e192\\u0026ndash;4.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eSteensma DP. Dysplasia has a differential diagnosis: distinguishing genuine myelodysplastic syndromes (MDS) from mimics, imitators, copycats and impostors. Curr Hematol Malig. 2012;7(4):310\\u0026ndash;20.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eHartung HD, Olson TS, Bessler M. Acquired aplastic anemia in children. Pediatr Clin North Am. 2013;60(6):1311\\u0026ndash;36.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eXu ZH. The bone morphological examination method for refractory anemia and megaloblasitc anemia[J]. World Clin Med 2016,10(6):239\\u0026ndash;40.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eChisholm KM, Bohling SD. Childhood Myelodysplastic Syndrome. Clin Lab Med. 2023;43(4):639\\u0026ndash;55.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eMalcovati L, Stevenson K, Papaemmanuil, E,Neuberg, D,Bejar. R,Boultwood J,etal.SF3B1-mutant MDS as a distinct disease subtype:a proposal from the International Working Group for the Prognosis of. MDS Blood. 2020;136(2):157\\u0026ndash;70.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eKhoury JD, Solary E, Abla O, Akkari Y, Alaggio R, Apperley JF et al. The 5th edition of the World Health Organization Classification of Haematolymphoid Tumors:Myeloid and Histiocytic/Dendritic Neoplasms.Leukemia.2022;36(7):1703\\u0026ndash;1719.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eTang L, Miao J, Wang J. Clinical characteristics of megaloblastic anemia with pancytopenia. Hematology. 2024;29(1):2420407.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eAslinia F, Mazza JJ, Yale SH. Megaloblastic anemia and other causes of macrocytosis[J]. Clin Med Res. 2006;4(3):236\\u0026ndash;41.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eZhang HD, Ma YJ, Liu QF, et al. Human erythrocyte lifespan measured by Levitt\\u0026prime;s CO breath test with newly developed automatic instrument. J Breath Res. 2018;12(3):036003.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eHtut TW, Thein KZ, Oo TH. Pernicious anemia: Pathophysiology and diagnostic difficulties. J Evid Based Med. 2021;14(2):161\\u0026ndash;9.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eEsposito G, Dottori L, Pivetta G, Ligato I, Dilaghi E, Lahner E. etal. Pernicious Anemia: The Hematological Presentation of a Multifaceted Disorder Caused by Cobalamin Deficiency. Nutrients. 2022;14(8):1672.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eNeumann WL, Coss E, Rugge M, Genta RM. Autoimmune atrophic gastritis\\u0026ndash;pathogenesis, pathology and management. Nat Rev Gastroenterol Hepatol. 2013;10(9):529\\u0026ndash;41.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eShen M, Luo X, Wu C, Wang J, Wang Z, Lei M. Meiqing Le Pernicious anemia is a common cause of cobalamin deficiency-caused megaloblastic anemia in Hainan. China Hematol. 2024;29(1):2399375.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eGreen R, Allen LH, Bj\\u0026oslash;rke-Monsen AL, Brito A, Gu\\u0026eacute;ant JL, Miller JW, Molloy AM, Nexo E, Stabler S, Toh BH, et al. Vitamin B12 deficiency. Nat Rev Dis Primers. 2017;3:17040.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eGreen R. Vitamin B12 deficiency from the perspective of a practicing hematologist.Blood. 2017;129(19):2603\\u0026ndash;11.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eSteinberg SE, Fonda S, Campbell C, Hillman RS. Cellular abnormalities of folate deficiency. Br J Haematol. 1983;54(4):605\\u0026ndash;12.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eStabler SP. Clinical practice. Vitamin B12 defi ciency. N Engl J Med. 2013;368(2):149\\u0026ndash;60.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eInfante M, Leoni M, Caprio M, Fabbri A. Long-term metformin therapy and vitamin B12 deficiency: An association to bear in mind. World J Diabetes 2021 July 15; 12(7): 916\\u0026ndash;31.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eVidal-Alaball J, Butler CC, Cannings-John R et al. Oral vitamin B12 versus intramuscular vitamin B12 for vitamin B12 deficiency. Cochrane Database Syst Rev. 2005;(3):CD004655.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eTandon R, Thacker J, Pandya U, Patel M, Tandon K. Parenteral vs Oral Vitamin B12 in Children With Nutritional Macrocytic Anemia: A Randomized Controlled Trial. Indian Pediatr. 2022;59(9):683\\u0026ndash;7. Epub 2022 May 31.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eHillman RS, Adamson J, Burka E. Characteristics of vitamin B12 correction of the abnormal erythropoiesis of pernicious anemia. Blood. 1968;31(4):419\\u0026ndash;32.\\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\":\"info@researchsquare.com\",\"identity\":\"bmc-pediatrics\",\"isNatureJournal\":false,\"hasQc\":true,\"allowDirectSubmit\":false,\"externalIdentity\":\"bped\",\"sideBox\":\"Learn more about [BMC Pediatrics](http://bmcpediatr.biomedcentral.com/)\",\"snPcode\":\"\",\"submissionUrl\":\"https://www.editorialmanager.com/bped/default.aspx\",\"title\":\"BMC Pediatrics\",\"twitterHandle\":\"BMC_series\",\"acdcEnabled\":true,\"dfaEnabled\":false,\"editorialSystem\":\"em\",\"reportingPortfolio\":\"BMC Series\",\"inReviewEnabled\":true,\"inReviewRevisionsEnabled\":true},\"keywords\":\"\",\"lastPublishedDoi\":\"10.21203/rs.3.rs-8467036/v1\",\"lastPublishedDoiUrl\":\"https://doi.org/10.21203/rs.3.rs-8467036/v1\",\"license\":{\"name\":\"CC BY 4.0\",\"url\":\"https://creativecommons.org/licenses/by/4.0/\"},\"manuscriptAbstract\":\"\\u003ch2\\u003eObjective\\u003c/h2\\u003e \\u003cp\\u003eTo investigate the etiology and diagnostic approach of pancytopenia in children, with emphasis on uncommon nutritional causes, particularly in individuals with intellectual disability, whose dietary behaviors may predispose them to deficiency. The goal is to reduce misdiagnosis and therapeutic delays in clinical practice.\\u003c/p\\u003e\\u003ch2\\u003eMethods\\u003c/h2\\u003e \\u003cp\\u003eWe retrospectively analyzed the clinical features, laboratory results, bone marrow findings, treatment, and outcomes of a child with trisomy 21 presenting with profound pancytopenia at Zaozhuang Municipal Hospital in November 2023, supplemented by a review of the literature.\\u003c/p\\u003e\\u003ch2\\u003eResults\\u003c/h2\\u003e \\u003cp\\u003eThe patient exhibited severe pancytopenia at admission with WBC\\u0026thinsp;=\\u0026thinsp;1.77\\u0026times;10⁹/L, RBC\\u0026thinsp;=\\u0026thinsp;0.47\\u0026times;10\\u0026sup1;\\u0026sup2;/L, hemoglobin\\u0026thinsp;=\\u0026thinsp;21 g/L, and platelets\\u0026thinsp;=\\u0026thinsp;5\\u0026times;10⁹/L. Bone marrow morphology, immunophenotyping, and serum folate/vitamin B12 assays confirmed megaloblastic anemia. Following folate and vitamin B12 replacement therapy, hematologic parameters progressively normalized.\\u003c/p\\u003e\\u003ch2\\u003eConclusion\\u003c/h2\\u003e \\u003cp\\u003eThe child was diagnosed with severe megaloblastic anemia (MA). MA typically causes macrocytic anemia and may lead to pancytopenia, although the case of profound pancytopenia with such severity is rare in the pediatric population in China. In cases with extremely low blood counts, differentiation from leukemia, myelodysplastic syndromes, and aplastic anemia is critical. Bone marrow aspiration and biopsy remain essential. Vitamin B12 deficiency in this case resulted in neuropsychiatric symptoms, including seizures, which improved substantially after vitamin replacement. This case underscores the importance of evaluating nutritional status in children with developmental delay and restricted dietary patterns.\\u003c/p\\u003e\",\"manuscriptTitle\":\"A Rare Case of Down Syndrome with Severe Pancytopenia: Clinical Analysis and Literature Review\",\"msid\":\"\",\"msnumber\":\"\",\"nonDraftVersions\":[{\"code\":1,\"date\":\"2026-01-28 01:28:16\",\"doi\":\"10.21203/rs.3.rs-8467036/v1\",\"editorialEvents\":[{\"type\":\"communityComments\",\"content\":0},{\"type\":\"decision\",\"content\":\"Revision requested\",\"date\":\"2026-02-16T06:50:51+00:00\",\"index\":\"\",\"fulltext\":\"\"},{\"type\":\"editorInvitedReview\",\"content\":\"\",\"date\":\"2026-02-13T21:24:03+00:00\",\"index\":\"hide\",\"fulltext\":\"\"},{\"type\":\"reviewerAgreed\",\"content\":\"236574689835338560801640794415734968307\",\"date\":\"2026-02-13T11:46:53+00:00\",\"index\":\"hide\",\"fulltext\":\"\"},{\"type\":\"reviewerAgreed\",\"content\":\"259680221751746173882732124960209839644\",\"date\":\"2026-02-11T21:35:18+00:00\",\"index\":\"hide\",\"fulltext\":\"\"},{\"type\":\"reviewerAgreed\",\"content\":\"22456966212322194031374542870809341811\",\"date\":\"2026-02-08T10:03:05+00:00\",\"index\":\"hide\",\"fulltext\":\"\"},{\"type\":\"editorInvitedReview\",\"content\":\"\",\"date\":\"2026-02-03T04:29:55+00:00\",\"index\":\"hide\",\"fulltext\":\"\"},{\"type\":\"reviewerAgreed\",\"content\":\"79802866081683575317234329712703755680\",\"date\":\"2026-01-24T22:13:56+00:00\",\"index\":\"hide\",\"fulltext\":\"\"},{\"type\":\"reviewerAgreed\",\"content\":\"310240652991315063935945756319147296665\",\"date\":\"2026-01-24T10:15:01+00:00\",\"index\":\"hide\",\"fulltext\":\"\"},{\"type\":\"reviewersInvited\",\"content\":\"\",\"date\":\"2026-01-22T08:33:57+00:00\",\"index\":\"\",\"fulltext\":\"\"},{\"type\":\"editorAssigned\",\"content\":\"\",\"date\":\"2026-01-22T07:09:46+00:00\",\"index\":\"\",\"fulltext\":\"\"},{\"type\":\"editorInvited\",\"content\":\"\",\"date\":\"2026-01-07T10:26:36+00:00\",\"index\":\"\",\"fulltext\":\"\"},{\"type\":\"checksComplete\",\"content\":\"\",\"date\":\"2026-01-07T07:40:52+00:00\",\"index\":\"\",\"fulltext\":\"\"},{\"type\":\"submitted\",\"content\":\"BMC Pediatrics\",\"date\":\"2026-01-07T07:27:33+00:00\",\"index\":\"\",\"fulltext\":\"\"}],\"status\":\"published\",\"journal\":{\"display\":true,\"email\":\"info@researchsquare.com\",\"identity\":\"bmc-pediatrics\",\"isNatureJournal\":false,\"hasQc\":true,\"allowDirectSubmit\":false,\"externalIdentity\":\"bped\",\"sideBox\":\"Learn more about [BMC Pediatrics](http://bmcpediatr.biomedcentral.com/)\",\"snPcode\":\"\",\"submissionUrl\":\"https://www.editorialmanager.com/bped/default.aspx\",\"title\":\"BMC Pediatrics\",\"twitterHandle\":\"BMC_series\",\"acdcEnabled\":true,\"dfaEnabled\":false,\"editorialSystem\":\"em\",\"reportingPortfolio\":\"BMC Series\",\"inReviewEnabled\":true,\"inReviewRevisionsEnabled\":true}}],\"origin\":\"\",\"ownerIdentity\":\"3d1630af-35e3-41ff-922d-e01a4c7f152f\",\"owner\":[],\"postedDate\":\"January 28th, 2026\",\"published\":true,\"recentEditorialEvents\":[],\"rejectedJournal\":[],\"revision\":\"\",\"amendment\":\"\",\"status\":\"under-review\",\"subjectAreas\":[],\"tags\":[],\"updatedAt\":\"2026-05-06T13:11:32+00:00\",\"versionOfRecord\":[],\"versionCreatedAt\":\"2026-01-28 01:28:16\",\"video\":\"\",\"vorDoi\":\"\",\"vorDoiUrl\":\"\",\"workflowStages\":[]},\"version\":\"v1\",\"identity\":\"rs-8467036\",\"journalConfig\":\"researchsquare\"},\"__N_SSP\":true},\"page\":\"/article/[identity]/[[...version]]\",\"query\":{\"redirect\":\"/article/rs-8467036\",\"identity\":\"rs-8467036\",\"version\":[\"v1\"]},\"buildId\":\"XKTyCvWXoU3ODBz1xrDgd\",\"isFallback\":false,\"isExperimentalCompile\":false,\"dynamicIds\":[84888],\"gssp\":true,\"scriptLoader\":[]}","source_license":"CC-BY-4.0","license_restricted":false}