Disease relevance of Leigh Disease

• Patient groups that included individuals with Leigh's disease, dystonia plus complex neurodegeneration, and Leber's hereditary optic neuropathy did not harbor the MTND6*LDYT14459A mutation, suggesting that this mutation displays a high degree of tissue specificity, thus producing a narrow phenotypic range [1].
• The more profound neurologic abnormalities include Leigh disease, spinocerebellar degeneration, and atypical Charcot-Marie-Tooth disease [2].
• The point mutation at bp 8993 of human mtDNA in the ATPase 6 gene is associated with neurogenic weakness, ataxia and retinitis pigmentosa, and with subacute necrotizing encephalomyelopathy (Leigh disease) when present at high copy number [3].
• The subunit pattern of COX is normal by immunoblot in patients with fatal myopathy and Leigh syndrome; a disproportionate decrease of subunit II was seen in a patient with myoclonic epilepsy with ragged red fibers [4].
• Optic neuropathy in Lhon and Leigh syndrome [5].

Psychiatry related information on Leigh Disease

• The author suggests that the histologic changes of Leigh's disease, as well as the similar changes of Wernicke's disease, could be due to a deficiency of cerebral thiamine triphosphate [6].

High impact information on Leigh Disease

• Leigh Syndrome (LS) is a severe neurological disorder characterized by bilaterally symmetrical necrotic lesions in subcortical brain regions that is commonly associated with systemic cytochrome c oxidase (COX) deficiency [7].
• We now report a mutation in the nuclear-encoded flavoprotein (Fp) subunit gene of the succinate dehydrogenase (SDH) in two siblings with complex II deficiency presenting as Leigh syndrome [8].
• Cycle sequencing of amplified NDUFS8 cDNA of 20 patients with isolated enzymatic complex I deficiency revealed two compound heterozygous transitions in a patient with neuropathologically proven Leigh syndrome [9].
• Mutations of SURF-1 in Leigh disease associated with cytochrome c oxidase deficiency [10].
• Leigh's disease due to a new mutation in the PDHX gene [11].

Chemical compound and disease context of Leigh Disease

• Defective activation of the pyruvate dehydrogenase complex in subacute necrotizing encephalomyelopathy (Leigh disease) [12].
• Brief treatment with dichloroacetate does not modify suspected subacute necrotizing encephalomyelitis [13].
• The large family of a 21-year-old man who died of Leigh disease was investigated for evidence of neurological abnormalities and presence of the adenosine triphosphate-thiamine diphosphate phosphoryltransferase inhibitor factor [14].
• We identified a single thymidine insertion at nucleotide position 5537 (T5537i) in the mitochondrial DNA transfer RNA gene for tryptophan in a family in which the proband had a progressive neurological disorder and his brother died in infancy of Leigh syndrome [15].
• Cytochrome c oxidase deficiency and long-chain acyl coenzyme A dehydrogenase deficiency with Leigh's subacute necrotizing encephalomyelopathy [16].

Biological context of Leigh Disease

• Impaired complex I assembly in a Leigh syndrome patient with a novel missense mutation in the ND6 gene [17].
• Genotyping microsatellite DNA markers at putative disease loci in inbred/multiplex families with respiratory chain complex I deficiency allows rapid identification of a novel nonsense mutation (IVS1nt -1) in the NDUFS4 gene in Leigh syndrome [18].
• Several of the MRP genes map to loci associated with disorders consistent with impaired oxidative phosphorylation, such as Leigh Syndrome, multiple mitochondrial dysfunctions, and non-syndromic hearing loss [19].
• Restriction enzyme analysis of the E1 alpha gene revealed that the mother was a heterozygote, indicating that thiamin-responsive PDHC deficiency associated with Leigh syndrome due to this mutation is transmitted by X-linked inheritance [20].
• Mutations in mtDNA were found in six out of eight children with Leigh syndrome, indicating a prevalent association between this phenotype and abnormalities in ND genes [21].

Anatomical context of Leigh Disease

• Deficiency of pyruvate dehydrogenase complex (PDHC) in Leigh's disease fibroblasts: an abnormality in lipoamide dehydrogenase affecting PDHC activation [22].
• Neuropathological study of a 3 1/2 year old girl with familial Leigh syndrome who also harboured a rare ATPase gene mutation disclosed extensive and unusual lesions in the cerebral cortex, despite a typical histological pattern [23].
• Some were discovered in French Canadians, such as autosomal recessive ataxia of the Charlevoix-Saguenay (MIM 270550), agenesis of corpus callosum and peripheral neuropathy (MIM 218000) and French-Canadian-type Leigh syndrome (MIM 220111) [24].
• Leukocyte DNA from 59 children with Leigh syndrome was screened for the T9176C mutation by conventional polymerase chain reaction methods [25].
• LAA in the frontal lobes and occipital lobes may be SPECT findings characteristic of Leigh syndrome and PEO, respectively [26].

Gene context of Leigh Disease

• Loss-of-function mutations of SURF1 cause Leigh syndrome associated with an isolated and generalized COX deficiency in humans [27].
• We report the first missense mutation within the nuclear encoded complex I subunit, NDUFS7, in 2 siblings with neuropathologically proven complex I-deficient Leigh syndrome [28].
• Leigh syndrome associated with mitochondrial complex I deficiency due to a novel mutation in the NDUFS1 gene [29].
• We report two novel pathogenic SURF1 mutations in a patient with Leigh syndrome and one novel SCO2 mutation in a patient with hypertrophic cardiomyopathy [30].
• The effect on the stability of alternative transcripts of different mutations of the NDUFS4 gene in patients with Leigh syndrome with complex I deficiency is presented [31].

Analytical, diagnostic and therapeutic context of Leigh Disease

• Biotinidase deficiency should be included in the differential diagnosis of Leigh syndrome and of unexplained respiratory problems [32].
• Positron emission tomography (PET) using pyruvate-1-11C was carried out to investigate the in vivo metabolism of pyruvate in the brains of patients with mitochondrial encephalomyopathy and Leigh's disease [33].

References