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Abstract

Introduction: Cobalamin C (cblC) deficiency represents a rare but treatable and potentially underrecognized cause of thrombotic microangiopathy (TMA) in both pediatric and adult populations. It is a multisystem disorder with heterogeneous clinical manifestations. TMA occurs in 10-25% of affected individuals. Case presentation: A ten-year-old girl presented with vomiting and abdominal pain, followed by generalized status epilepticus and hypertensive crisis. Neuroimaging was unremarkable. Laboratory evaluation demonstrated severe renal impairment (creatinine 506 µmol/L), microangiopathic hemolysis and thrombocytopenia. Atypical hemolytic uremic syndrome (aHUS) was suspected and treated with eculizumab and intermittent hemodialysis. Genetic analysis identified biallelic pathogenic variants in the MMACHC gene, confirming cblC deficiency. Metabolic treatment (parenteral hydroxocobalamin, betaine, L-carnitine, and folinic acid) was initiated promptly. During the clinical course, the patient experienced relapses of hypertensive crises despite stable metabolic parameters and well-controlled fluid balance. Blood pressure control required a regimen of six antihypertensive agents, and renal replacement therapy was administered for ten weeks. At follow-up, blood pressure and renal function have improved (eGFR 60 mL/min/1.73 m², Schwartz formula), and no neurological sequelae were observed. Conclusion: CblC deficiency should be considered in all pediatric cases of atypical hemolytic uremic syndrome (aHUS). Measurement of plasma total homocysteine and/or methylmalonic acid in blood or urine, followed by molecular genetic confirmation, is essential to avoid diagnostic delay. Early initiation of targeted metabolic therapy can substantially improve renal outcomes and survival. Conclusion: Diagnosis and CI referral in Thailand occurred well beyond internationally recommended ages, and age-group differences in non-verbal performance were observed, underscoring the need to strengthen early hearing detection and referral systems.

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