title: A Korean female patient with thiamine-responsive pyruvate dehydrogenase complex deficiency due to a novel point mutation (Y161C)in the PDHA1 gene.
abstract: Pyruvate dehydrogenase complex (PDHC) deficiency is mostly due to mutations in the X-linked E1alpha subunit gene (PDHA1). Some of the patients with PDHC deficiency showed clinical improvements with thiamine treatment. We report the results of biochemical and molecular analysis in a female patient with lactic acidemia. The PDHC activity was assayed at different concentrations of thiamine pyrophosphate (TPP). The PDHC activity showed null activity at low TPP concentration (1 x 10(-3) mM), but significantly increased at a high TPP concentration (1 mM). Sequencing analysis of PDHA1 gene of the patient revealed a substitution of cysteine for tyrosine at position 161 (Y161C). Thiamine treatment resulted in reduction of the patient's serum lactate concentration and dramatic clinical improvement. Biochemical, molecular, and clinical data suggest that this patient has a thiamine-responsive PDHC deficiency due to a novel mutation, Y161C. Therefore, to detect the thiamine responsiveness it is necessary to measure activities of PDHC not only at high but also at low concentration of TPP.
authors.affiliation: Department of Pediatrics and Research Laboratory for Human Mitochondrial Disorders, Ajou University School of Medicine, Suwon, Korea.
authors.forename: Eun-Ha
authors.initials: EH
authors.lastname: Lee
authors.forename: Mi-Sun
authors.initials: MS
authors.lastname: Ahn
authors.forename: Jin-Soon
authors.initials: JS
authors.lastname: Hwang
authors.forename: Kyung-Hwa
authors.initials: KH
authors.lastname: Ryu
authors.forename: Sun-Jun
authors.initials: SJ
authors.lastname: Kim
authors.forename: Sung-Hwan
authors.initials: SH
authors.lastname: Kim
mesh_terms: D002478:Cells, Cultured; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D017354:Point Mutation; D030481:Pyruvate Dehydrogenase (Lipoamide) / Q000235:genetics*; D015325:Pyruvate Dehydrogenase Complex Deficiency Disease / Q000188:drug therapy / Q000235:genetics*; D013831:Thiamine / Q000627:therapeutic use*; D013835:Thiamine Pyrophosphate / Q000378:metabolism
chemical_list: D030481:Pyruvate Dehydrogenase (Lipoamide); C065640:pyruvate dehydrogenase E1alpha subunit; D013835:Thiamine Pyrophosphate; D013831:Thiamine