title: Leukoencephalopathy with accumulated succinate is indicative of SDHAF1 related complex II deficiency.
abstract: BACKGROUND
  Deficiency of complex II (succinate dehydrogenase, SDH) represents a rare cause of mitochondrial disease and is associated with a wide range of clinical symptoms. Recently, mutations of SDHAF1, the gene encoding for the SDH assembly factor 1, were reported in SDH-defective infantile leukoencephalopathy. Our goal was to identify SDHAF1 mutations in further patients and to delineate the clinical phenotype.
  
  
  METHODS
  In a retrospective data collection study we identified nine children with biochemically proven complex II deficiency among our cohorts of patients with mitochondrial disorders. The cohort comprised five patients from three families affected by SDH-defective infantile leukoencephalopathy with accumulation of succinate in disordered cerebral white matter, as detected by in vivo proton MR spectroscopy. One of these patients had neuropathological features of Leigh syndrome. Four further unrelated patients of the cohort showed diverse clinical phenotypes without leukoencephalopathy. SDHAF1 was sequenced in all nine patients.
  
  
  RESULTS
  Homozygous mutations of SDHAF1 were detected in all five patients affected by leukoencephalopathy with accumulated succinate, but not in any of the four patients with other, diverse clinical phenotypes. Two sisters had a mutation reported previously, in three patients two novel mutations were found.
  
  
  CONCLUSIONS
  Leukoencephalopathy with accumulated succinate is a key symptom of defective complex II assembly due to SDHAF1 mutations.
authors.affiliation: Department of Pediatrics and Pediatric Neurology, Georg August University, Robert Koch Str, 40, Göttingen, 37075, Germany. aohlenb@gwdg.de
authors.forename: Andreas
authors.initials: A
authors.lastname: Ohlenbusch
authors.forename: Simon
authors.initials: S
authors.lastname: Edvardson
authors.forename: Johannes
authors.initials: J
authors.lastname: Skorpen
authors.forename: Alf
authors.initials: A
authors.lastname: Bjornstad
authors.forename: Ann
authors.initials: A
authors.lastname: Saada
authors.forename: Orly
authors.initials: O
authors.lastname: Elpeleg
authors.forename: Jutta
authors.initials: J
authors.lastname: Gärtner
authors.forename: Knut
authors.initials: K
authors.lastname: Brockmann
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D056784:Leukoencephalopathies / Q000235:genetics / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D011506:Proteins / Q000235:genetics*; D019802:Succinic Acid / Q000378:metabolism*
chemical_list: D011506:Proteins; C553227:SDHAF1 protein, human; D019802:Succinic Acid