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Pyruvate dehydrogenase complex deficiency: Biochemical and immunoblot analysis of cultured skin fibroblasts
Author(s) -
Old Susan E.,
de Vivo Darryl C.
Publication year - 1989
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.410260610
Subject(s) - pyruvate dehydrogenase complex , polyclonal antibodies , western blot , protein subunit , microbiology and biotechnology , biology , isozyme , isocitrate dehydrogenase , dehydrogenase , antibody , gene , medicine , biochemistry , endocrinology , enzyme , genetics
Abstract Cultured skin fibroblasts were obtained from 11 children with lactic acidemia and neurological disturbances. The residual activities of pyruvate dehydrogenase complex were 9 to 45% of control values in all specimens. Immunoblot analysis of mitochondrial proteins using polyclonal antibodies against the alpha and beta subunits of the first component (E 1 ) of the pyruvate dehydrogenase complex revealed markedly decreased amounts of cross‐reacting material in 4 boys who died in infancy. Two of the boys were half brothers related through a common mother. A fifth boy had an alteration of the electrophoretic mobility of the E 1 α subunit and normal E 1 β subunit abundance. The remaining 6 patients (2 boys and 4 girls) had normal findings on Western blot assay, and all 11 patients had normal E 2 and E 3 patterns. These findings suggest that the E 1 α subunit gene represents a genetically vulnerable site on the X chromosome. Decreased abundance of E 1 components appears to be associated with death in infancy. A normal Western blot analysis is compatible with long‐term survival despite decreased catalytic activity of the pyruvate dehydrogenase complex.