ADENINE-NUCLEOTIDE TRANSLOCATOR DEFICIENCY IN MUSCLE - POTENTIAL THERAPEUTIC VALUE OF VITAMIN-E

The major function of mitochondria is to provide energy in the form of ATP and creatine phosphate to enable cells and tissues to drive cellu lar energy-requiring functions. The biochemical defects in mitochondri al energy metabolism can be classified into four groups: (1) defects i n oxidative phosphorylation, (2) defects in mitochondrial dehydrogenas es, (3) defects in mitochondrial transport processes and (4) defects i n mitochondrial enzymes catalysing the synthesis of oxidative substrat es (non-redox reactions) (Scholte 1988). Most of the patients sufferin g from these defects have increased lactate levels and/or abnormal con centrations of organic acids in their body fluids. Usually, one of mor e of the enzymes involved in mitochondrial energy production is found to be deficient. Increased lactate is the sole finding in patients wit h defects in oxidative phosphorylation, or a deficiency of pyruvate de hydrogenase or pyruvate carboxylase. In a previous paper we described in detail a now 8-year-old boy with strongly increased lactate levels but impressively increased activities of all enzyme complexes of the r espiratory chain and the pyruvate dehydrogenase complex. Immunostainin g of Western blots revealed that he suffers from a muscle-specific def iciency of his mitochondrial adenine nucleotide translocator (Bakker e t al 1993). In the present paper we describe the effects of treatment with vitamin E. This therapy appears to be effective, as judged from c linical investigations. In vivo P-31-NMR spectroscopy of the muscle co nfirmed the clinical improvement.