NEUROLOGICAL PRESENTATIONS OF MITOCHONDRIAL DISEASES

We present here a report on a 5-year experience in clinical investigat ion, diagnostic management and molecular genetic studies of neuromitoc hondrial disorders, defined on the basis of morphological, biochemical and genetic findings. Leigh disease is the most frequent clinical pre sentation in infancy and childhood, but symptoms al onset are poorly i nformative. In paediatric cases, lactic acidosis and neuroradiological abnormalities are frequent, and can be of help for the diagnostic ori entation. In the adult population, muscle weakness, ophthalmoplegia wi th ragged-red fibres, retinitis pigmentosa, progressive myoclonal atax ia, and early-onset stroke-like episodes, are frequently combined in c omplex syndromes that are often familial (maternally inherited) and/or associated with well-established mutations in mitochondrial DNA (mtDN A). However, the presence of overlap syndromes and features common to many neuromitochondrial diseases can complicate the clinical evaluatio n and the diagnostic approach, The pathogenicity of a given mtDNA muta tion can frequently be ascertained by correlating the degree of hetero plasmy with the clinical or biochemical phenotypes. Moreover, transmit ochondrial cybrids can be used to test the effects of either mitochond rial or nuclear gene abnormalities in a fully controlled, user-friendl y and highly informative system.