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MMADHC gene
Reviewed by Medicinsk Expert•Last updated: 2026-10-22•Gene

MMADHC gene

The MMADHC gene provides instructions for making a protein essential for the metabolism of vitamin B12, facilitating its conversion into vital cofactors within the cell.

Normal Function

The MMADHC gene provides instructions for making a protein that helps convert vitamin B12 (also called cobalamin) into one of two molecules: adenosylcobalamin (AdoCbl) or methylcobalamin (MeCbl).

AdoCbl is a cofactor required for the normal function of the enzyme methylmalonyl CoA mutase, which helps break down certain amino acids, fatty acids, and cholesterol. MeCbl is a cofactor for the enzyme methionine synthase, which converts the amino acid homocysteine to methionine, a building block for proteins and other important compounds.

Research indicates that the MMADHC protein plays a role in the final steps of AdoCbl and MeCbl formation. Working with the MMACHC protein, MMADHC transports vitamin B12 to specific regions of the cell: the mitochondria (where AdoCbl functions) or the cytoplasm (where MeCbl functions).

Health Conditions Related to Genetic Changes

Homocystinuria

Variants in the MMADHC gene can cause homocystinuria, characterized by developmental delay, neurological problems, eye defects, and blood abnormalities. These variants result in a protein that cannot transport vitamin B12 to the cytoplasm. The resulting shortage of MeCbl impairs methionine synthase, leading to a buildup of homocysteine in the bloodstream and a depletion of methionine.

Methylmalonic acidemia

Variants in the MMADHC gene are also linked to methylmalonic acidemia, a condition characterized by feeding difficulties, metabolic crises (low blood glucose and toxic buildup in the blood), and long-term health problems. These variants prevent the transport of vitamin B12 to the mitochondria, impairing the function of methylmalonyl CoA mutase and causing toxic compounds to accumulate in organs and tissues.

Methylmalonic acidemia with homocystinuria

Variants can cause methylmalonic acidemia with homocystinuria, cblD type, which features symptoms of both conditions described above. The resulting protein cannot transport vitamin B12 to either the mitochondria or the cytoplasm, disrupting the production of both AdoCbl and MeCbl. This dual defect leads to the buildup of toxic compounds and a decrease in methionine production.

Other Names for This Gene

  • C2orf25
  • cblD
  • CL25022
  • methylmalonic aciduria (cobalamin deficiency) cblD type, with homocystinuria
  • methylmalonic aciduria and homocystinuria type D protein, mitochondrial
  • methylmalonic aciduria and homocystinuria type D protein, mitochondrial precursor
  • methylmalonic aciduria and homocystinuria, cblD type
  • MMAD_HUMAN

Frequently Asked Questions

Typical red‑flag symptoms include poor feeding, vomiting, lethargy, rapid breathing, and a sudden drop in blood glucose. Laboratory findings during a crisis show markedly elevated plasma methylmalonic acid, metabolic acidosis, and sometimes hyperammonemia. Prompt emergency treatment with intravenous fluids, glucose, and parenteral vitamin B12 can prevent organ damage.
MMADHC mutations follow an autosomal‑recessive pattern: both parents must carry one pathogenic copy to have an affected child. Each pregnancy carries a 25 % chance of being affected, a 50 % chance of the child being a carrier, and a 25 % chance of being unaffected and not a carrier. Carrier testing for the parents and prenatal diagnostic options (chorionic villus sampling or amniocentesis with targeted MMADHC analysis) can be discussed with a genetic counselor.
clinician will usually order a plasma amino acid panel and a urine organic acid analysis, which show elevated methylmalonic acid. If these results suggest a cobalamin‑responsive disorder, targeted sequencing of the MMADHC gene (often as part of a broader cobalamin‑metabolism panel) is performed. In some labs, whole‑exome or whole‑genome sequencing can also detect MMADHC variants.
Yes, many patients respond to intramuscular or high‑dose oral hydroxocobalamin, which bypasses the transport defect and raises intracellular methylcobalamin levels. Regular monitoring of plasma homocysteine, methionine, and vitamin B12 concentrations guides dosing. Early treatment often improves growth, neurodevelopment, and reduces the risk of thrombotic events, but lifelong supplementation is usually required.
Source: MedlinePlus, National Library of Medicine

MedlinePlus brings together authoritative health information from the National Library of Medicine (NLM), the National Institutes of Health (NIH), and other government agencies and health-related organizations.

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