PRESENTATION AND CLINICAL INVESTIGATION OF MITOCHONDRIAL RESPIRATORY-CHAIN DISEASE - A STUDY OF 51 PATIENTS

Defects of the mitochondrial respiratory chain are associated with a g reat variety of clinical disorders. Whilst recognition of these condit ions is increasing, the need for sophisticated biochemical and molecul ar studies has tended to limit both their investigation and diagnosis to a few specialist centres. Using a group of 51 patients with histoch emically, biochemically and/or genetically defined respiratory chain d efects, we have examined both the clinical heterogeneity of these diso rders and how they may be investigated most effectively in non-special ist centres. We evaluated the use of the following routinely available clinical investigations-fasting intermediary metabolites (lactate, py ruvate, ketone bodies, etc.) in blood and cerebrospinal fluid, serum c reatine kinase estimation EMG, EEC, CT MRI and histological/histochemi cal muscle biopsy analysis. Our studies show that, in addition to well -recognized syndromes (e.g. chronic progressive external ophthalmopleg ia, mitochondrial encephalopathy lactic acidosis and stroke like episo des, and myoclonus epilepsy with ragged red-fibres, a significant numb er of patients present with non-specific encephalopathic disorders, Fu rthermore, even within those categories of respiratory chain disease w hich have been genetically defined, a wide variation of presenting sym ptoms and signs were found, Where there was initial doubt concerning t he diagnosis, the following clinical features were helpful in suggesti ng respiratory chain disease: ophthalmoplegia; a maternal pattern of i nheritance; the presence of myopathy or deafness in association with e ncephalopathy. Of the clinical investigations we assessed, elevated la ctate in blood or cerebrospinal fluid and low density lesions in the b asad ganglia were helpful in identifying patients with respiratory cha in dysfunction. Histochemical analysis of muscle was, however the sing le most useful investigation being diagnostic in patients with chronic progressive external ophthalmoplegia, Kearns-Sayre syndrome and myopa thy, and of significant importance in patients presenting primarily wi th central nervous system disease. The results of our study are used t o discuss the most appropriate approach to diagnosis of this group of disorders.