A child with cobalamin C deficiency caused by complex heterozygous variation of c.567dupT and c.80A > G complicated with pulmonary arterial hypertension and hydrocephalus: A case report and literature review

RATIONALE: Cobalamin C (cblC) deficiency is one of the most common congenital vitamin B12 metabolic abnormalities, and may cause severe neurologic symptoms, gastrointestinal and nephritic symptoms. PATIENT CONCERNS: A 9-month-old boy presented with a 10-day history of progressive dyspnea and weak cough, accompanied by moaning, perioral cyanosis, and poor feeding. The parents also reported significant developmental regression and delay, characterized by an inability to raise his head, sit independently, or vocalize "dada" and "mama": milestones typically achieved by this age. DIAGNOSIS: The patient was diagnosed with cblCdeficiency, complicated by combined methylmalonic acidemia and homocystinuria, based on clinical manifestations (developmental regression, cyanosis, pulmonary arterial hypertension (PAH)) and confirmatory genetic testing (compound heterozygous variants in the methylmalonic aciduria cobalamin deficiency type C with homocystinuria gene: c.567dupT and c.80A > G). INTERVENTIONS: Following admission, the patient received multifaceted treatment. Metabolic therapy included hydroxocobalamin, folic acid, betaine, and L-carnitine to address the methylmalonic acidemia and homocystinuria. Antibiotic therapy with cefotaxime was administered for concurrent pneumonia. Additionally, bosentan (64 mg/day) was initiated for the management of PAH. OUTCOMES: At discharge, the patient exhibited stable vital signs, improved developmental milestones, reduced pulmonary artery systolic pressure, normal renal function, and no evidence of hydrocephalus progression. Genetic analysis revealed a genotype-phenotype correlation: the c.567dupT variant was associated with neurodevelopmental disorders and early-onset severe disease, whereas the c.80A > G variant correlated with PAH and renal dysfunction. LESSONS: This report highlights the diverse clinical manifestations of cblC deficiency based on specific methylmalonic aciduria cobalamin deficiency type C with homocystinuria mutations. A review of the literature supports these genotype-phenotype associations, aiding in prognostic stratification and targeted management.