Chronic leigh disease: A genetic and biochemical study

Abstract

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. Of 217 persons (seven generations) included in the pedigree, 68 were examined neurologically and biochemically. Fourteen (20%), 5 of whom had abnormal neurological findings, were found to excrete the inhibitor factor. Clinical manifestations varied from severe neurological affliction to subtle deficits. A chronic relapsing course was frequently encountered, with exacerbations occurring in association with apparent metabolic stress. Parental consanguinity was identified in the propositus as well as in other family members with neurological abnormalities. Males and females were affected, and no vertical transmission of the trait was found. These multigenerational data suggest that Leigh disease in adults is inherited in an autosomal recessive manner and has variable degrees of expression with a wide spectrum of neurological manifestations.

Subacute necrotizing encephalomyelopathy (Leigh syndrome) associated with disturbed oxidation of pyruvate, malate and 2-oxoglutarate in muscle and liver

“…Leigh syndrome can be transmitted as an autoso-ma1 recessive trait (34). It is likely, therefore, that this patient's brother, though presenting with a different clinical picture, also suffered from SNE.…”

The Use of a Computerised Database for the Diagnosis of a Rare Neurological Syndrome

“…Cataracts may be associated with Leigh's disease but are unusual. Plaitakis et al (14) reported a man aged 21 years and 7 of his relatives with chronic Leigh's disease. The transmission in the family was compatible with autosomal dominant inheritance.…”

Síndrome de Leigh: relato de caso

“…Múltiplos defeitos genéticos, como pontos de mutação envolvendo a transcrição T-G e T-C na posição 8993 ou transição A-G na posição 8344, têm sido descritos associados a esta síndrome, provocando alteração do complexo piruvato desidrogenase, assim como dos cinco complexos que constituem a cadeia respiratória, sendo que a deficiência do citocromo C oxidase (complexo IV), provocada por mutações tanto de genes mitocondriais quanto nuclear, é o mais freqüentemente afetado nesta síndrome, sendo que a transmissão genética relacionada com o DNA mitocondrial é a mais comum (2)(3)(9)(10) .…”

“…É uma enfermidade neurometabólica congênita, que faz parte do grupo das encefalopatias mitocondriais. Sabe-se que a alteração ocorre no metabolismo energético, sendo a principal causa de defeito na fosforilação oxidativa e geração de ATP celular (2)(3) . Existem três tipos de transmissão genética associada a esta síndrome: herança recessiva ligada ao X, mitocondrial e autossômica recessiva (4) .…”