The clinical picture of early-onset cobalamin C defect (methylmalonic aciduria and homocystinuria)

Cobalamin C defect is a rare inborn error of intracellular cobalamin metabolism characterised by methylmalonic aciduria and homocystinuria. The early-onset form is a multi-systemic disorder with poor neurological outcome. Treatment is based on a combined approach aimed at improving metabolic abnormalities. We report details of clinical findings in a series of 11 patients with cobalamin C defect in whom onset of symptoms occurred within the first month of life. At onset, all patients presented with at least five major clinical signs including feeding difficulties (11/11), hypotonia (11/11), haematological abnormalities (10/11), failure to thrive (9/11), microcephaly (9/11), coma/lethargy (7/11), seizures (6/11), hydrocephalus (5/11), cardiomyopathy (3/11), haemolytic uremic syndrome (2/11), atrophic gastritis (2/11). Two died at the time of diagnosis.At follow-up (age range 7 months–15 years, mean 5.9 years) the main signs were: developmental delay/mental retardation (9/9), nystagmus/visual impairment (8/9), abnormal behaviour (4/9), epilepsy (4/9). Our report underlines the multi-system involvement at onset. After the start of therapy we observed the disappearance of visceral and haematological signs in almost all cases but with no apparent beneficial effect on the neurological symptoms, since mental retardation was invariably present.