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.

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Journal European Journal of Human Genetics
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Hellebrekers, D.M.E.I, Sallevelt, S.C.E.H, Theunissen, T.E.J. (Tom E.J.), Hendrickx, A, Gottschalk, R.W. (Ralph W), Hoeijmakers, J.G.J, … Smeets, H.J.M. (2017). Novel SLC25A32 mutation in a patient with a severe neuromuscular phenotype. European Journal of Human Genetics, 25(7), 886–888. doi:10.1038/ejhg.2017.62