Methylmalonic Aciduria and Homocystinuria, Cobalamin C Type (MMACHC)
Methylmalonic aciduria and homocystinuria, cobalamin C type is a pan-ethnic, autosomal recessive disease caused by pathogenic variants in the MMACHC gene. The clinical features are variable, and onset may be in infancy, childhood or adolescence. The most common presentation is during the first year of life. Affected infants are often born small and have a failure to thrive. Symptoms include lethargy, seizures and ataxia, and progressive encephalopathy. Affected infants also have characteristic facial features and may have cardiac malformations. Early-onset cases are associated with a poor prognosis and early death. Alternatively, onset may be in adolescence, where patients exhibit neuropsychiatric manifestations including psychosis and dementia. Several specific variants are associated with the development of either the early or later-onset form, but some variants do not have a known genotype-phenotype correlation.
For information about carrier frequency and residual risk, please see the residual risk table.