Defects of Mitochondrial DNA

In the past few years several syndromes have been associated with lesions of the human mitochondrial DNA. MtDNA is a small, circular extra‐nuclear chromosome encoding essential components of the respiratory chain. MtDNA‐related syndromes can be divided into two groups: mitochondrial encephalomyopathies, characterized by the presence of ragged‐red fibres (RRF) as the morphological hallmark, or “pure” encephalopathies with no gross morphological abnormalities in muscle. The first group includes myoclonic epilepsy with ragged‐red fibres (MERRF), mitochondrial encephalomyopathy with lactic acidosis and stroke‐like episodes (MELAS), Kearns‐Sayre syndrome (KSS), chronic progressive external ophthalmoplegia (CPEO) and a new entity, maternally inherited myopathy and cardiomyopathy. The second group includes Leber's Hereditary Optic Neuroretinopathy (LHON) and the newly described ataxia‐retinitis pigmentosa‐dementia complex. Three kinds of molecular lesions have been identified: point mutations of protein encoding mtDNA‐genes (similar to yeast mit‐ mutations); point mutations of mtDNA‐tRNA genes (similar to yeast syn‐ mutations); and large‐scale rearrangements of mtDNA (similar to yeast ρ‐ mutations). In general, “mit‐” mutations are responsible for non‐RRF encephalopathies, while “syn‐” and “ρ‐” mutations are associated with mitochondrial encephalomyopathies with RRF. Furthermore, point mutations [mit‐ and syn‐) are usually maternally‐ inherited, while large‐scale mtDNA rearrangements are either sporadic or inherited as mendelian traits. In most cases, the molecular detection of the known defects of mtDNA can be carried out by non‐invasive techniques, thus making it an easy and relatively inexpensive procedure in the differential diagnosis of the mitochondrial disorders, a rapidly expanding area of clinical neurology. Copyright © 1992, Wiley Blackwell. All rights reserved