Clinical features of 51 patients confirmed with mitochondrial respiratory chain disease and clinical investigations most helpful in diagnosis of different phenotypes are reported from the Divisions of Clinical Neuroscience and Neurobiology, University of Newcastle upon Tyne, UK. Ages ranged from birth to 55 years, and 21 patients were <16 years. Presenting symptoms in order of frequency included ptosis and ophthalmoplegia (20), lactic acidosis (10), seizures (6), myopathy (6), failure to thrive (6), and ataxia (5). Features other than ptosis and ophthalmoplegia identified as clues to respiratory chain dysfunction were as follows: 1) lactic acidosis with deafness, short stature/failure to thrive, or basal ganglia calcifications on CT; 2) family history of neurological disease with maternal transmission; and 3) proximal myopathy and CNS disease. In addition to well-recognized syndromes (MERRF and MELAS) many had non-specific encephalopathies. The most useful confirmatory diagnostic test was histochemical analysis of muscle. [1]

COMMENT. Mitochondrial respiratory chain disease is manifested by a large variety of syndromes, but histological and chemical analysis of skeletal muscle is frequently diagnostic. Succinate dehyrogenase, cytochrome c oxidase activity, and DNA studies in muscle may be performed on a needle biopsy specimen. Elevated CSF lactate is a good indicator of mitochondrial disease in patients with encephalopathic disorders.

The treatment of congenital lactic acidosis is reviewed from the Center for Inherited Disorders of Energy Metabolism, Case Western Reserve University, Cleveland, OH [2]. Treatments have included diet, vitamins, use of enzyme activators, and enzyme replacement. None has been very successful.

See Progress in Pediatric Neurology I and II (Millichap JG, Ed. PNB Publ, 1991 and 1994) for further articles on mitochondrial cytopathies. The diagnosis of mitochondrial disorder should be considered with the following: 1) an unexplained association of symptoms; 2) an early onset and rapidly progressive course; and 3) involvement of unrelated organs sharing no common embryologic origin and no common biological functions.