The Novel Mutation p.Asp251Asn in the β-subunit of succinate-CoA Ligase Causes Encephalomyopathy and Elevated Succinylcarnitine

J Hum Genet. 2013 Aug;58(8):526-30. doi: 10.1038/jhg.2013.45. Epub 2013 Jun 13.

Abstract

SUCLA2 is one of several nuclear-encoded genes that can cause encephalomyopathy accompanied by mitochondrial DNA depletion. The disorder usually manifests in early childhood and leads to early death. The gene encodes one of the subunits of succinyl-CoA synthase, the enzyme that catalyzes the reversible conversion of substrates succinyl-CoA and ADP to products succinate and ATP in the tricarboxylic acid pathway. Thirty-two individuals harboring mutations in SUCLA2 have so far been reported, and five different mutations were observed among these individuals. Here we report identification of a novel mutation in SUCLA2 in two cousins affected with encephalomyopathy. The novel mutation causes p.Asp251Asn; the affected amino acid is likely positioned within the ATP-grasp domain of the encoded protein. As previously reported in other patients, we did not observe elevation of methylmalonic acid, the biochemical hallmark of patients with mutations in SUCLA2. We instead found elevated levels of succinylcarnitine.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Amino Acid Substitution / genetics*
  • Brain / pathology
  • Carnitine / analogs & derivatives*
  • Carnitine / metabolism*
  • Child
  • Child, Preschool
  • Female
  • Humans
  • Infant
  • Infant, Newborn
  • Magnetic Resonance Imaging
  • Male
  • Mitochondrial Encephalomyopathies / enzymology*
  • Mutation / genetics*
  • Pedigree
  • Succinate-CoA Ligases / chemistry
  • Succinate-CoA Ligases / genetics*

Substances

  • Succinate-CoA Ligases
  • SUCLA2 protein, human
  • Carnitine