title: Leigh syndrome caused by mutations in the flavoprotein (Fp) subunit of succinate dehydrogenase (SDHA).
abstract: Detailed clinical, neuroradiological, histological, biochemical, and genetic investigations were undertaken in a child suffering from Leigh syndrome. The clinical symptoms started at age five months and led to a severe progressive neurodegenerative disorder causing epilepsy, psychomotor retardation, and tetraspasticity. Biochemical measurement of skeletal muscle showed a severe decrease in mitochondrial complex II. Sequencing of SDHA revealed compound heterozygosity for a nonsense mutation in exon 4 (W119X) and a missense mutation in exon 3 (A83V), both absent in normal controls. In six additional patients--five with Leigh or Leigh-like syndrome and one with neuropathy and ataxia associated with isolated deficiency of complex II--mutations in SDHA were not detected, indicating genetic heterogeneity.
authors.affiliation: Metabolic Disease Centre Munich-Schwabing, Institute of Clinical Chemistry, Academic Hospital Schwabing, Kölner Platz 1, 80804 Munich, Germany. Rita.Horvath@lrz.uni-muenchen.de
authors.forename: R
authors.initials: R
authors.lastname: Horváth
authors.forename: A
authors.initials: A
authors.lastname: Abicht
authors.forename: E
authors.initials: E
authors.lastname: Holinski-Feder
authors.forename: A
authors.initials: A
authors.lastname: Laner
authors.forename: K
authors.initials: K
authors.lastname: Gempel
authors.forename: H
authors.initials: H
authors.lastname: Prokisch
authors.forename: H
authors.initials: H
authors.lastname: Lochmüller
authors.forename: T
authors.initials: T
authors.lastname: Klopstock
authors.forename: M
authors.initials: M
authors.lastname: Jaksch
mesh_terms: D001284:Atrophy / Q000473:pathology; D001706:Biopsy; D001921:Brain / Q000473:pathology; D002540:Cerebral Cortex / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D004247:DNA / Q000032:analysis; D018076:DNA, Complementary / Q000032:analysis; D018450:Disease Progression; D005091:Exons / Q000235:genetics; D005260:Female; D005420:Flavoproteins / Q000235:genetics*; D007839:Functional Laterality; D006801:Humans; D015151:Immunoblotting; D007223:Infant; D007888:Leigh Disease / Q000175:diagnosis / Q000235:genetics*; D008279:Magnetic Resonance Imaging; D008297:Male; D018482:Muscle, Skeletal / Q000473:pathology; D017354:Point Mutation / Q000235:genetics*; D016133:Polymerase Chain Reaction; D021122:Protein Subunits / Q000235:genetics*; D012313:RNA / Q000032:analysis; D013385:Succinate Dehydrogenase / Q000235:genetics*
chemical_list: D018076:DNA, Complementary; D005420:Flavoproteins; D021122:Protein Subunits; D012313:RNA; D004247:DNA; D013385:Succinate Dehydrogenase