MITOCHONDRIAL DISORDERS

Mitochondria, the organelles devoted to energy production, have unique genetic features. They possess their own genome encoding several subu nits of the respiratory chain, the majority of which are encoded by nu clear DNA, as well as factors involved in replication, transcription a nd translation of mitochondrial DNA. In the past few years, molecular lesions of mitochondrial DNA have been reported with increasing freque ncy as a source of human disorders. Several mutations of mitochondrial DNA, either as sporadic large scale rearrangements (deletions, duplic ations) or maternally-inherited point mutations, have been associated with well defined clinical syndromes. Furthermore, because of the nucl ear DNA contribution to the synthesis of respiratory chain enzymes, ph enotypes transmitted as Mendelian traits have also been identified and associated with qualitative (multiple deletions) and quantitative (de pletion) lesions of the mitochondrial genome. The clinical manifestati ons of mitochondrial DNA mutations are extremely heterogeneous, rangin g from myopathies, encephalomyopathies, cardiopathies, to complex mult isystem syndromes. Clinical, morphological, biochemical and molecular genetic data are necessary for diagnosis. The recent advances in genet ic studies provide both diagnostic tools and new pathogenetic insights into this rapidly expanding area of human pathology.