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

MMACHC gene

The MMACHC gene provides instructions for a protein that processes vitamin B12 into essential cofactors required for breaking down proteins and fats and for converting homocysteine to methionine.

Normal Function

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

  • AdoCbl is a cofactor for 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.

The MMACHC protein processes different forms of vitamin B12 and interacts with the MMADHC protein to transport the vitamin to the regions of the cell where these cofactors are needed: the mitochondria (for AdoCbl) or the cytoplasm (for MeCbl).

Health Conditions Related to Genetic Changes

Methylmalonic acidemia with homocystinuria

Dozens of MMACHC gene variants cause methylmalonic acidemia with homocystinuria, cblC type, the most common form of a disorder characterized by developmental delay, eye defects, neurological problems, and blood abnormalities. These variants lead to a nonfunctional MMACHC protein, preventing the normal processing and transport of vitamin B12.

Because both AdoCbl and MeCbl are missing, the enzymes that require them do not function normally. This results in:

  • A buildup of toxic compounds, including homocysteine.
  • A decrease in the production of methionine.
  • The inability to properly break down certain amino acids, fatty acids, and cholesterol.

Other Names for This Gene

  • cblC
  • DKFZP564I122
  • methylmalonic aciduria (cobalamin deficiency) cblC type, with homocystinuria
  • methylmalonic aciduria and homocystinuria type C protein

Frequently Asked Questions

Diagnosis typically involves measuring elevated plasma methylmalonic acid and homocysteine levels, low methionine, and confirming elevated urinary methylmalonic acid. Genetic testing of the MMACHC gene (sequencing or targeted mutation analysis) is then performed to identify pathogenic variants.
cute metabolic decompensation may present with vomiting, lethargy, rapid breathing, seizures, or sudden worsening of neurologic function. If any of these occur, seek immediate medical care; emergency labs (blood gases, ammonia, lactate, methylmalonic acid) guide rapid intervention with IV hydroxocobalamin and supportive measures.
Each pregnancy carries a 25 % chance of an affected child, a 50 % chance of a carrier, and a 25 % chance of an unaffected non‑carrier. Options such as preimplantation genetic testing for monogenic disease (PGT‑M) with IVF, prenatal diagnostic testing (CVS or amniocentesis), or use of donor gametes can be discussed with a genetics counselor.
Standard therapy combines high-dose hydroxocobalamin (usually 1 mg intramuscularly daily or several times per week), betaine to lower homocysteine, folate, and sometimes carnitine. Treatment is lifelong and should be started as early as possible to improve neurodevelopmental outcomes.
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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