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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.
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.
Nutritional
A severe nutritional deficiency of vitamin B12 can also result in methylmalonic acidemia.[3] Methylmalonyl CoA mutase 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]
Genotypes
Online 'Mendelian Inheritance in Man' (OMIM) 251100 - cblA type
Online 'Mendelian Inheritance in Man' (OMIM) 251110 - cblB type
Online 'Mendelian Inheritance in Man' (OMIM) 277400 - cblC type
Online 'Mendelian Inheritance in Man' (OMIM) 277410 - cblD type
Online 'Mendelian Inheritance in Man' (OMIM) 277380 - cblF type
Online 'Mendelian Inheritance in Man' (OMIM) 606169 - cblH type
Online 'Mendelian Inheritance in Man' (OMIM) 251000 - mut type
^ 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. PMID 16763906.
^ 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.
^ 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.
^ http://www.biology.arizona.edu/biochemistry/problem_sets/b12/04t.html Vitamin B12 deficiency - The methylmalonic aciduria connection
Organic Acidemia Association
Overview of condition at NLM Genetics Home Reference
