Methylmalonic acidemia is an inherited metabolic disorder in which the body cannot process certain proteins and fats properly, leading to a buildup of toxic substances in the body and metabolic crises.
Symptoms typically appear in early infancy and can vary from mild to life-threatening. Individuals with this condition often experience vomiting, dehydration, weak muscle tone (hypotonia), developmental delay, lethargy, enlarged liver (hepatomegaly), and failure to thrive. Long-term complications of this disorder can include feeding problems, intellectual disability, chronic kidney disease, and inflammation of the pancreas. In more severe cases, this disorder can lead to coma and death if left untreated. Treatment is focused on managing symptoms, and includes aggressive management of decompensation events, a low-protein diet, certain medications and antibiotics, and in some cases, liver, and kidney transplantation.
This condition is caused by pathogenic (disease-causing) variants in several different genes and the testing we provide covers the MMAA, MMAB, and MMUT genes. They all exhibit autosomal recessive inheritance, which means that both parents must be carriers to have a 25% chance to have a child with the condition. The risk of being a carrier is based on a person’s ancestry or ethnic background. Carriers typically do not experience any symptoms of the disorder.
The age of onset typically relates to the causative gene with the MMAA gene (a.k.a, cblA type) onsetting anywhere from the infancy or early childhood, the MMAB gene (a.k.a., cblB type) onsetting shortly after birth, and the MMUT gene also onsetting shortly after birth and being the most severe form of the disorder.
Resources:
Genetic and Rare Diseases Information Center (GARD)
Revised November 2023
