Infant cobalamin C deficiency linked to severe vascular complications

A four-month-old Chinese girl developed atypical hemolytic uremic syndrome and life-threatening pulmonary arterial hypertension in a case report documenting an unusually severe vascular presentation of cobalamin C deficiency. The inherited disorder, caused by biallelic pathogenic variants in the MMACHC gene, impaired the intracellular processing of vitamin B12 and produced marked biochemical abnormalities. After treatment with metabolic therapy and cardiopulmonary support, her pulmonary hypertension resolved within one week, while her blood and kidney abnormalities normalized within two weeks.

The infant had severe hyperhomocysteinemia, measured at 124.4 μmol/L, and elevated urinary methylmalonic acid. Her serum ammonia was normal at 36 μmol/L, and she had mild hypoargininemia at 24 μmol/L. These findings were consistent with cobalamin C deficiency, a condition described as the most common inherited disorder of intracellular cobalamin metabolism. Genetic analysis revealed compound heterozygous variants in MMACHC: c.80 A > G, which produced p.Q27R, and c.658_660delAAG, which produced p.K220del.

Clinically, the simultaneous occurrence of atypical hemolytic uremic syndrome and pulmonary arterial hypertension represented an extremely rare and life-threatening phenotype. The report did not provide a broader comparison group or establish why this infant developed such severe complications. As a single-patient case report, it cannot determine the frequency of the combined presentation, demonstrate that the two variants caused each complication in general, or support population-level estimates of risk. The authors nevertheless noted that the c.80 A > G/c.658_660delAAG genotype has been strongly associated with early-onset, devastating vascular complications in Chinese infants, an association that requires evidence beyond this individual case.

The infant’s outcome improved rapidly under a multidisciplinary approach that combined metabolic therapy with cardiopulmonary support. Pulmonary arterial hypertension resolved completely within one week, and hematologic and renal parameters returned to normal within two weeks. She remained clinically stable and showed age-appropriate neurodevelopment at three years of age after 45 months of continuous follow-up. The long-term observation is encouraging, although it does not mean that every child with the same diagnosis will have an equally favorable course.

The family’s subsequent pregnancy was tested prenatally, and the authors reported detection of a heterozygous c.80 A > G variant in the fetus. The newborn sibling was described as having normal development, but the supplied report does not establish a longer-term clinical outcome for that child. The investigators recommended that clinicians consider screening for cobalamin C deficiency in infants with unexplained atypical hemolytic uremic syndrome or pulmonary arterial hypertension, based on the possibility that early recognition and treatment could prevent severe deterioration.

Subject of Research: A case report of infantile cobalamin C deficiency with atypical hemolytic uremic syndrome and pulmonary arterial hypertension.

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

Article References: Wan, L., Tu, J., Li, H., Wang, X., & Chen, C. (2026). A case report of cobalamin C deficiency presenting with atypical hemolytic uremic syndrome and life-threatening pulmonary arterial hypertension in a Chinese infant. BMC Pediatrics. https://doi.org/10.1186/s12887-026-07889-x

Image Credits: AI Generated

DOI: 10.1186/s12887-026-07889-x

Keywords: cobalamin C deficiency, infant disease, atypical hemolytic uremic syndrome, pulmonary arterial hypertension, MMACHC, metabolic disorder, genetic diagnosis, case report, case, report, cobalamin, deficiency