Novel SLC25A32 mutation in a patient with a severe neuromuscular phenotype

Eur J Hum Genet. 2017 Jun;25(7):886-888. doi: 10.1038/ejhg.2017.62. Epub 2017 Apr 26.


In a 51-year-old patient of consanguineous parents with a severe neuromuscular phenotype of early-onset ataxia, myoclonia, dysarthria, muscle weakness and exercise intolerance, exome sequencing revealed a novel homozygous variant (c.-264_31delinsCTCACAAATGCTCA) in the mitochondrial FAD-transporter gene SLC25A32. Flavin adenine dinucleotide (FAD) is an essential co-factor for many mitochondrial enzymes and impaired mitochondrial FAD-transport was supported by a reduced oxidative phosphorylation complex II activity in the patient's muscle, decreased ATP production in fibroblasts, and a deficiency of mitochondrial FAD-dependent enzymes. Clinically, the patient showed improvement upon riboflavin treatment, which is a precursor of FAD. Our results confirm the recently reported case of SLC25A32 as a cause of riboflavin-responsive disease. Our patient showed a more severe clinical phenotype compared with the reported patient, corresponding with the (most likely) complete absence of the SLC25A32-encoding MFT (Mitochondrial Folate Transporter) protein.

Publication types

  • Case Reports

MeSH terms

  • Ataxia / diagnosis
  • Ataxia / drug therapy
  • Ataxia / genetics*
  • Cells, Cultured
  • Dysarthria / diagnosis
  • Dysarthria / drug therapy
  • Dysarthria / genetics*
  • Fibroblasts / metabolism
  • Humans
  • INDEL Mutation*
  • Male
  • Membrane Transport Proteins / genetics*
  • Middle Aged
  • Muscle Weakness / diagnosis
  • Muscle Weakness / drug therapy
  • Muscle Weakness / genetics*
  • Phenotype
  • Riboflavin / metabolism
  • Riboflavin / therapeutic use
  • Syndrome
  • Vitamin B Complex / metabolism
  • Vitamin B Complex / therapeutic use


  • Membrane Transport Proteins
  • SLC25A32 protein, human
  • Vitamin B Complex
  • Riboflavin