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.









Disease Name
 GeneGuaranteed Exons 
 Inheritance Ethnicity
 Carrier Frequency
 Detection Rate
Residual Risk

Methylmalonic Aciduria and Homocystinuria, Cobalamin C TypeMMACHC1-4 [4] (*9)ARCaucasian1 in 13870%0.00218340611353712
Methylmalonic Aciduria and Homocystinuria, Cobalamin C TypeMMACHC1-4 [4] (*9)ARAsian1 in 11376%0.00213675213675214
Methylmalonic Aciduria and Homocystinuria, Cobalamin C TypeMMACHC1-4 [4] (*9)ARWorldwide1 in 13870%0.00218340611353712