DEFECT IN THE LIPOYL-BEARING PROTEIN-X SUBUNIT OF THE PYRUVATE-DEHYDROGENASE COMPLEX IN 2 PATIENTS WITH ENCEPHALOMYELOPATHY

Among the many metabolic encephalomyelopathies caused by deficiencies in the pyruvate dehydrogenase complex (PDHC), nearly all involve its E 1 subunit. We describe two new familial cases of PDHC deficiency with encephalomyelopathy, chronic lactic acidemia, and a normol E1 subunit of PDHC but deficiency in another component. Activity of PDHC was meas ured in cultured skin fibroblasts and skeletal muscle, and immunoblot studies were performed on mitochondrial extracts from skin fibroblasts . Spectra of muscle tissue, obtained in vivo with phosphorus 31 nuclea r magnetic resonance, were recorded both at rest and with exercise. Th e PDHC activity was markedly reduced to 10% to 20% of normal values in both cultured skin fibroblasts and skeletal muscle. Immunoblotting of skin fibroblast mitochondrial extracts showed a specific deficiency i n the protein X component of PDHC but normal E1, E2, and E3 components . Spectra obtained with P-31 nuclear magnetic resonance showed alterat ions compatible with those found in mitochondrial myopathies. This is the second description of an encephalomyelopathy associated with a spe cific absence of the lipoyl-containing protein X component, which has a structural role in the formation of a functional PDHC.