Methylmalonic acidemia

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Methylmalonic acidemia
Classification and external resources
Methylmalonic acid
ICD-10 E71.1
ICD-9 270.3
DiseasesDB 29509 29510
MedlinePlus 001162
eMedicine neuro/576 

Methylmalonic acidemia ("MMA"), also called methylmalonic aciduria, is an autosomal genetic disorder affecting branched-chain amino acids. It is a classical type of organic acidemia.[1]

Methylmalonic acidemia is diagnosed in the early neonatal period, presenting progressive encephalopathy and secondary hyperammonemia. The disorder does not always result in death, if kept under control.

Contents

[edit] Causes

[edit] Genetic

The inherited form of methylmalonic acidemia causes a defect in the metabolic pathway where methylmalonyl-coenzyme A (CoA) is converted into succinyl-CoA by the enzyme methylmalonyl-CoA mutase.[2]

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.

[edit] Nutritional

A severe nutritional deficiency of vitamin B12 can also result in methylmalonic acidemia.[3] 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.[4]

[edit] Genotypes

[edit] See also

[edit] References

  1. ^ Dionisi-Vici C, Deodato F, Raschinger W, Rhead W, Wilcken B (2006). "Classical organic acidurias, propionic aciduria, methylmalonic aciduria, and isovaleric aciduria: long-term outcome and effects of expanded newborn screening using tandem mass spectrometry". J Inherit Metab Dis. 29 (2-3): 383-389. doi:10.1007/s10545-006-0278-z. PMID 16763906. 
  2. ^ Sakomoto O, Ohura T, Matsubara Y, Takayanagi M, Tsuchiya S (2007). "Mutation and haplotype analyses of the MUT gene in Japanese patients with methylmalonic acidemia". J Hum Genet. 52 (1): 48-55. PMID 17075691. 
  3. ^ Higginbottom MC, Sweetman L, Nyhan WL (1978). "A syndrome of methylmalonic aciduria, homocystinuria, megaloblastic anemia and neurological abnormalities in a vitamin B12-deficient breast-fed infant of a strict vegitarian". N Engl J Med. 299 (7): 317-323. PMID 683264. 
  4. ^ http://www.biology.arizona.edu/biochemistry/problem_sets/b12/04t.html
    Vitamin B12 deficiency - The methylmalonic aciduria connection

[edit] External links

v • d • e
Inborn errors of amino acid metabolism (E70-72, 270)
K
Lysine/straight chain
G→pyruvate
G→alpha-ketoglutarate
G→succinyl-CoA
General BC/OA
Propionic acidemia - Methylmalonic acidemia
G→fumarate
G→oxaloacetate
Transport
Tyrosine→Melanin
Glycine→Creatine
Other
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