A case report of cobalamin C deficiency presenting with atypical hemolytic uremic syndrome and life-threatening pulmonary arterial hypertension in a Chinese infant

Abstract

Cobalamin C (cblC) deficiency is the most common inherited disorder of intracellular cobalamin metabolism, resulting from biallelic pathogenic variants in the MMACHC gene. Concurrent atypical hemolytic uremic syndrome (aHUS) and pulmonary arterial hypertension (PAH) constitutes an extremely rare but life-threatening vascular phenotype. We present a 4-month-old Chinese female infant who manifested simultaneous aHUS and life-threatening PAH. Laboratory examinations showed severe hyperhomocysteinemia (124.4 µmol/L), elevated urinary methylmalonic acid, normal serum ammonia (36 µmol/L), and mild hypoargininemia (24 µmol/L). Genetic analysis identified compound heterozygous MMACHC variants c.80 A > G (p.Q27R) and c.658_660delAAG (p.K220del). Combined metabolic therapy and cardiopulmonary support led to complete resolution of PAH within 1 week and normalization of hematologic and renal parameters within 2 weeks. The patient remained clinically stable with age-appropriate neurodevelopment at 3 years of age during 45 months of continuous follow-up. Prenatal genetic testing in a subsequent pregnancy detected a heterozygous c.80 A > G variant, and the newborn sibling has shown normal development. This case demonstrates that early multidisciplinary intervention can achieve excellent long-term outcomes even in severe infantile cblC deficiency with combined aHUS and PAH. The MMACHC c.80 A > G/c.658_660delAAG genotype is strongly associated with early-onset devastating vascular complications in Chinese infants. We recommend that clinicians prioritize cblC deficiency screening in all infants with unexplained aHUS or PAH.

The authors' abstract, as published at the source. BMC Pediatrics, 2026 · DOI ↗