A novel SCARB2 mutation in progressive myoclonus epilepsy indicated by reduced β-glucocerebrosidase activity

J Neurol Sci. 2014 Apr 15;339(1-2):210-3. doi: 10.1016/j.jns.2014.01.022. Epub 2014 Jan 23.

Abstract

Action myoclonus renal failure (AMRF) syndrome is a rare form of progressive myoclonus epilepsy with renal dysfunction related to mutations in the SCARB2 gene. This gene is involved in lysosomal mannose-6-phosphate-independent trafficking of β-glucocerebrosidase (GC), an enzyme deficient in Gaucher disease. We report a family with myoclonic epilepsy, ataxia and skeletal muscle atrophy but without cognitive impairment or overt renal disease. A novel SCARB2 mutation was indicated by a striking discrepancy between lymphocyte and fibroblast GC activity in the proband evaluated for possible Gaucher disease. Our findings expand the genetic and phenotypic diversity of AMRF and suggest that low GC activity may present an important biochemical clue to the diagnosis of AMRF.

Keywords: Action myoclonus renal failure syndrome; Ataxia; Gaucher disease; LIMP2; Progressive myoclonus epilepsy; SCARB2.

Publication types

  • Case Reports

MeSH terms

  • Adolescent
  • Enzyme Activation / physiology
  • Follow-Up Studies
  • Glucosylceramidase / metabolism*
  • Humans
  • Lysosomal Membrane Proteins / genetics*
  • Male
  • Mutation / genetics*
  • Myoclonic Epilepsies, Progressive / diagnosis
  • Myoclonic Epilepsies, Progressive / enzymology*
  • Myoclonic Epilepsies, Progressive / genetics*
  • Pedigree
  • Receptors, Scavenger / genetics*

Substances

  • Lysosomal Membrane Proteins
  • Receptors, Scavenger
  • SCARB2 protein, human
  • Glucosylceramidase