Leigh’s syndrome

Leigh s syndrome (subacute necrotizing encephalomyelopathy) is characterized by a variable combination of clinical abnormalities including cerebellar ataxia, developmental delay, mental regression, deafness, optic atrophy, hypotonia, and... 

Defects of complex II. These have not been fully characterized in the few reported patients, and the diagnosis has often been based solely on a decrease of succinate-cytochrome c reductase activity (Fig. 42-3). However, partial complex II deficiency was documented in muscle and cultured fibroblasts from two sisters with clinical and neuroradiological evidence of Leigh s syndrome, and molecular genetic analysis showed that both patients were homozygous for a point mutation in the flavoprotein subunit of the complex [17]. This was the first documentation of a molecular defect in the nuclear genome associated with a respiratory chain disorder. 

Defects of complex III. Like defects of complex I, these can be due to nDNA mutations or to mtDNA mutations. The only nuclear defect described thus far does not affect a complex III subunit, but an ancillary protein needed for proper assembly, BCS1L. Mutations in BCS1L can cause a Leigh s-syndrome-like disorder or a fatal infantile disease called GRACILE (growth retardation, aminoaciduria, cholestasis, iron overload, lactacidosis, and early death). 

LSD lysergic acid diethylamide inherited Leigh s syndrome... 

Mattews PM, Marchington DR, Squier M, Land J, Brown R, Brown GK. Molecular genetic characterization of an X-linked form of Leigh s syndrome. Ann Neurol 1993 33 652-5. 

Mildly deleterious base substitutions 2. Moderately deleterious nucleotide substitutions 3. Severe nucleotide substitutions Familial deafness, Alzheimer s disease, Parkinson s disease Leber s Hereditary Optic Neuropathy (LHON), Myoclonic Epilepsy and Ragged-Red Fiber disease (MERRF) Leigh s Syndrome dystonia... 

Some forms of Leigh s syndrome are caused by PDH dysfunction (Chapter 11). 

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