mut0 methylmalonic acidemia: eleven novel mutations of the methylmalonyl CoA mutase including a deletion-insertion mutation

Hum Mutat. 2000 Aug;16(2):179. doi: 10.1002/1098-1004(200008)16:2<179::AID-HUMU17>3.0.CO;2-R.


Methylmalonic aciduria (MMA) is an autosomal-recessive disorder caused by inadequate function of methylmalonyl-CoA mutase (MCM), a nuclear-encoded, mitochondrial enzyme that uses adenosylcobalamin as a cofactor. Biochemical cell studies have delineated phenotypic variants: mut(0) phenotypes in which there is no detectable enzymatic activity and mut- phenotypes in which there is residual cobalamin-dependent activity. Mutation screening in MMA has led to the detection of 30 disease-specific mutations. In 14 patients with the mut(0) phenotype we found 11 novel mutations (K54X, A137V, F174S, 620insA, G203R, Q218H, A535P, H627R, 2085delG and 2270del4/ins5), 6 of them homozygous, consisting of 1 nonsense, 6 missense, 1 splice site, and 3 frame shift mutations. The position in relation to different functional domains in MCM allow for an interpretation of the identified mutations. Hum Mutat 16:179, 2000.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Gene Deletion*
  • Humans
  • Infant, Newborn
  • Lipid Metabolism, Inborn Errors / enzymology*
  • Lipid Metabolism, Inborn Errors / genetics*
  • Methylmalonic Acid / metabolism*
  • Methylmalonyl-CoA Mutase / genetics*
  • Mutagenesis, Insertional / genetics*
  • Mutation / genetics*
  • Phenotype


  • Methylmalonic Acid
  • Methylmalonyl-CoA Mutase