Methylmalonic aciduria

Methylmalonic acidemia
Classification and external resources
10 9 OMIM DiseasesDB MedlinePlus eMedicine neuro/576

Methylmalonic acidemia (MMA), also called methylmalonic aciduria, is an autosomal recessive[1] metabolic disorder.[2] It is a classical type of organic acidemia.[3]

Methylmalonic acidemia stems from several genotypes,[4] all forms of the disorder usually diagnosed in the early neonatal period, presenting progressive encephalopathy, and secondary hyperammonemia. The disorder can result in death if undiagnosed or left untreated.

Causes

Genetic



The inherited forms of methylmalonic acidemia cause defects in the metabolic pathway where methylmalonyl-coenzyme A (CoA) is converted into succinyl-CoA by the enzyme methylmalonyl-CoA mutase.[5]

Vitamin B12 is also needed for the conversion of methylmalonyl-CoA to Succinyl-CoA. Mutations leading to defects in vitamin B12 metabolism or in its transport frequently result in the development of methylmalonic acidemia.

This disorder has an autosomal recessive inheritance pattern, which means the defective gene is located on an autosome, and two copies of the gene—one from each parent—must be inherited to be affected by the disorder. The parents of a child with an autosomal recessive disorder are carriers of one copy of the defective gene, but are usually not affected by the disorder.

Nutritional

A severe nutritional deficiency of vitamin B12 can also result in methylmalonic acidemia.[6] Methylmalonyl CoA requires vitamin B12 to form succinyl-CoA. When the amount of B12 is insufficient for the conversion of cofactor methylmalonyl-CoA into succinyl-CoA, the buildup of unused methylmalonyl-CoA eventually leads to methylmalonic acidemia. This diagnosis is often used as an indicator of vitamin B12 deficiency in serum.[7]

Pathogenesis

Methylmalonic acidemia has varying diagnoses, treatment requirements and prognoses, which are determined by the specific genetic mutation causing the inherited form of the disorder.[4] The following are the known genotypes responsible for methylmalonic acidemia:

OMIM Name Gene
251100 cblA type MMAA
251110 cblB type MMAB
277400 cblC type MMACHC
277410 cblD type MMADHC[8]
277380 cblF type LMBRD1[9]
251000 mut type MUT

See also

References

External links

  • Organic Acidemia Association
  • NLM Genetics Home Reference
  • Washington Health Center
  • GeneReviews article on Methylmalonic Acidemia
  • GeneReviews article on Disorders of Intracellular Cobalamin Metabolism
  • [1]
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