Horváth, R.; Klopstock, Thomas; Jaksch, M.; Holinski-Feder, E.; Abicht, Angela; Lochmüller, Hans; Laner, A.; Gempel, K.; Prokisch, H.
Leigh syndrome caused by mutations in the flavoprotein (Fp) subunit of succinate dehydrogenase (SDHA).
In: Journal of Neurology, Neurosurgery & Psychiatry, Vol. 77, No. 1: pp. 74-76
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.