A variant of uncertain significance in SDHAF1, the succinate dehydrogenase chaperone protein, in an adult patient with spastic paraparesis and leukoencephalopathy

Mult Scler Relat Disord. 2021 Sep:54:103132. doi: 10.1016/j.msard.2021.103132. Epub 2021 Jul 3.

Abstract

Succinate dehydrogenase (SDH), or respiratory complex II, consists of four nuclear-encoded subunits. The chaperone protein succinate dehydrogenase assembly factor 1 (SDHAF1) plays an essential role in the assembly of SDH, and in the incorporation of iron-sulfur clusters into the SDHB subunit. SDHB couples the oxidation of succinate to fumarate with the reduction of ubiquinone (coenzyme Q) to ubiquinol. Previously reported mutations in SDHAF1 have been associated with infantile leukoencephalopathy. We report an adult case with a homozygous variant of uncertain significance (VUS) mutation in SDHAF1, presenting with dementia, spastic paraparesis, and cardiomyopathy, initially diagnosed as multiple sclerosis.

Keywords: Leukoencephalopathy; Multiple sclerosis; Respiratory chain; Succinate dehydrogenase assembly factor 1.

Publication types

  • Case Reports
  • Letter

MeSH terms

  • Adult
  • Humans
  • Leukoencephalopathies* / complications
  • Leukoencephalopathies* / diagnostic imaging
  • Leukoencephalopathies* / genetics
  • Molecular Chaperones
  • Mutation
  • Paraparesis, Spastic*
  • Proteins / genetics
  • Succinate Dehydrogenase / genetics
  • Succinate Dehydrogenase / metabolism

Substances

  • Molecular Chaperones
  • Proteins
  • SDHAF1 protein, human
  • Succinate Dehydrogenase