Methylmalonic acidemia with homocystinuria is a disorder in which the body is unable to correctly process certain protein building blocks (amino acids), fat building blocks (fatty acids), and  cholesterol. The body is also unable to convert the amino acid homocysteine to another amino acid, methionine. Individuals with this disorder have a combination of features from two separate conditions, methylmalonic acidemia and homocystinuria. There are several forms of this combined condition, and the different forms have different genetic causes and signs and symptoms. The most common and best understood form, called cblC type (or cobalamin C disease), occurs in about 80 percent of affected individuals.

Methylmalonic acidemia with homocystinuria can be caused by variants (also known as mutations) in one of several genes, including MMACHC, MMADHC, LMBRD1, and ABCD4. Variants in these genes account for the different types of the disorder: cblC, cblD, cblF, and cblJ, respectively. Another type, called epi-cblC, is caused by variants in the PRDX1 gene, usually in combination with an MMACHC gene variant.

The most common form of the condition, methylmalonic acidemia with homocystinuria, cblC type, is estimated to affect 1 in 200,000 newborns worldwide. This form of the condition may be even more common in certain populations; some studies estimate that it occurs in 1 in 100,000 people in New York and 1 in 60,000 people in California.

Methylmalonic acidemia with homocystinuria is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell must have a variant to cause the disorder. The parents of an individual with an autosomal recessive condition each carry one copy of the altered gene, but they typically do not show signs and symptoms of the condition.

Published Date: May 16, 2023
Published By: National Institutes of Health