IN-VIVO FUNCTIONAL INVESTIGATIONS OF LACTIC-ACID IN PATIENTS WITH RESPIRATORY-CHAIN DISORDERS

Objective-To assess the prevalence of in vivo detectable abnormalities of lactate metabolism in mitochondrial disorders. Design-Retrospectiv e study in a metabolic investigation unit. Patients-28 patients with a respiratory chain disorder identified from biochemical or genetic ana lyses, or both, and 133 age matched controls. Controls were children i n whom causes of secondary hyperlactataemia and/or disorders, affectin g the energy pathways could be excluded. Methods-Lactate and pyruvate were measured in blood, together with other intermediary metabolism in dices, before and one hour after four meals each day. Lactate and crea tinine in a 24 hour urine sample collected at the same time were analy sed. When basal hyperlactataemia was not evident, an intravenous gluco se or pyruvate loading test was performed as a provocative test. Resul ts-Abnormal lactate metabolism was found in 25 of 28 patients thus dem onstrating the potential usefulness of these investigations in the dia gnosis of mitochondrial diseases. Moderate lactate accumulation was pr esent in relatively mild disease, associated with a mitochondrial DNA mutation and combined respiratory complexes deficiency. By contrast, h igh lactate concentrations were observed in very young children, with severe disease, isolated complex deficiency, and no apparent mitochond rial DNA defect.