Methylmalonic acidemia

Methylmalonic acidemia
Classification and external resources
Methylmalonic acid
ICD-10	E71.1
ICD-9	270.3
OMIM	251000 251100 251110 277380 277400 277410 606169
DiseasesDB	29509 29510
MedlinePlus	001162
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.

Contents 1 Causes 1.1 Genetic 1.2 Nutritional 2 Pathogenesis 3 See also 4 References 5 External links

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

• Isovaleric acidemia
• Propionic acidemia
• Maple syrup urine disease

References

External links

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

Inborn error of amino acid metabolism (E70–E72, 270) K→acetyl-CoA Lysine/straight chain Glutaric acidemia type 1 · type 2 · Hyperlysinemia · Pipecolic acidemia · Saccharopinuria Leucine Maple syrup urine disease · Isovaleric acidemia · 3-Methylcrotonyl-CoA carboxylase deficiency · 3-hydroxy-3-methylglutaryl-CoA lyase deficiency · 3-Methylglutaconic aciduria 1 Tryptophan Hypertryptophanemia G G→pyruvate→citrate Glycine Sarcosinemia · D-Glyceric acidemia · Glutathione synthetase deficiency Glycine→Creatine: GAMT deficiency · Glycine encephalopathy G→glutamate→ α-ketoglutarate Histidine Carnosinemia · Histidinemia · Urocanic aciduria Proline Hyperprolinemia · Prolidase deficiency Glutamate/glutamine SSADHD G→propionyl-CoA→ succinyl-CoA Valine Maple syrup urine disease · Hypervalinemia · Isobutyryl-CoA dehydrogenase deficiency Isoleucine Maple syrup urine disease · Beta-ketothiolase deficiency · 2-Methylbutyryl-CoA dehydrogenase deficiency Methionine Hypermethioninemia · Homocystinuria · Cystathioninuria General BC/OA Propionic acidemia · Methylmalonic acidemia · Methylmalonyl-CoA mutase deficiency G→fumarate Phenylalanine/tyrosine Phenylketonuria Tetrahydrobiopterin deficiency · 6-Pyruvoyltetrahydropterin synthase deficiency Tyrosinemia Type II tyrosinemia · Type III tyrosinemia/Hawkinsinuria · Alkaptonuria/Ochronosis · Type I tyrosinemia Tyrosine→Melanin Albinism: Ocular albinism (1) · Oculocutaneous albinism (Hermansky–Pudlak syndrome) · Waardenburg syndrome Tyrosine→Norepinephrine Dopamine beta hydroxylase deficiency · reverse: Brunner syndrome G→oxaloacetate Urea cycle/Hyperammonemia (arginine, aspartate) N-Acetylglutamate synthase deficiency · Carbamoyl phosphate synthetase I deficiency · Ornithine transcarbamylase deficiency/translocase deficiency · Citrullinemia · Argininosuccinic aciduria · Argininemia Transport/ IE of RTT Solute carrier family: Cystinuria · Hartnup disease · Lysinuric protein intolerance · Iminoglycinuria Fanconi syndrome: Oculocerebrorenal syndrome · Cystinosis Other Trimethylaminuria · 2-Hydroxyglutaric aciduria · Fumarase deficiency M: MET mt, k, c/g/r/p/y/i, f/h/s/l/o/e, a/u, n, m k, cgrp/y/i, f/h/s/l/o/e, au, n, m, epon m(A16/C10),i(k, c/g/r/p/y/i, f/h/s/o/e, a/u, n, m)

Metabolic disorders of vitamins, coenzymes, and cofactors B7 Biotin/MCD Biotinidase deficiency · Holocarboxylase synthetase deficiency Other B B5 (Pantothenate kinase-associated neurodegeneration) · B12 (Methylmalonic acidemia) Other vitamin Familial isolated vitamin E deficiency Nonvitamin cofactor Tetrahydrobiopterin deficiency · Molybdenum cofactor deficiency M: NUT cof, enz, met noco, nuvi, sysi/epon, met drug(A8/11/12)