Riboflavin responsive mitochondrial myopathy is a new phenotype of dihydrolipoamide dehydrogenase deficiency. The chaperon-like effect of vitamin B2

Mitochondrion. 2014 Sep:18:49-57. doi: 10.1016/j.mito.2014.09.006. Epub 2014 Sep 22.

Abstract

Dihydrolipoamide dehydrogenase (DLD, E3) is a flavoprotein common to pyruvate, α-ketoglutarate and branched-chain α-keto acid dehydrogenases. We found two novel DLD mutations (p.I40Lfs*4; p.G461E) in a 19 year-old patient with lactic acidosis and a complex amino- and organic aciduria consistent with DLD deficiency, manifesting progressive exertional fatigue. Muscle biopsy showed mitochondrial proliferation and lack of DLD cross-reacting material. Riboflavin supplementation determined the complete resolution of exercise intolerance with the partial restoration of the DLD protein and disappearance of mitochondrial proliferation in the muscle. Morphological and functional studies support the riboflavin chaperon-like role in stabilizing DLD protein with rescue of its expression in the muscle.

Keywords: Branched-chain amino acids; Chaperon; Dihydrolipoamide dehydrogenase deficiency; Mitochondrial myopathy; Riboflavin; α-Keto acids.

Publication types

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

MeSH terms

  • Acidosis, Lactic / complications*
  • Acidosis, Lactic / therapy*
  • Biopsy
  • Gene Expression / drug effects
  • Humans
  • Male
  • Maple Syrup Urine Disease / complications*
  • Maple Syrup Urine Disease / therapy*
  • Mitochondrial Myopathies / pathology*
  • Mitochondrial Myopathies / therapy*
  • Muscles / pathology
  • Phenotype
  • Protein Stability / drug effects
  • Riboflavin / administration & dosage*
  • Vitamin B Complex / administration & dosage*
  • Young Adult

Substances

  • Vitamin B Complex
  • Riboflavin

Supplementary concepts

  • Lactic Acidosis, Congenital Infantile, Due To LAD Deficiency