title: Concomitant administration of sodium dichloroacetate and thiamine in west syndrome caused by thiamine-responsive pyruvate dehydrogenase complex deficiency.
abstract: We treated a female patient with West syndrome caused by thiamine-responsive pyruvate dehydrogenase complex (PDHC) deficiency. Infantile spasms occurred in association with elevated blood and CSF lactate concentrations; these symptoms disappeared when lactate concentrations had been lowered by treatment with concomitant sodium dichloroacetate (DCA) and high dose thiamine. Sequencing the patient's PDHC E(1)alpha subunit revealed a substitution of serine for glycine at position 89 in exon 3 (G89S). This mutation must be a de novo mutation because it was not found in either parents' genome DNA. To our knowledge, five previously described patients with PDHC deficiency have displayed the West syndrome. All six known patients, including our own, were female, even though an approximately equal number of males and females have been identified with PDHC deficiency and overall West syndrome occurs somewhat more frequently in males. These results indicated that West syndrome occurred more frequently in female patients with PDHC deficiency. It is suggested that lactate concentration should be measured in patients with West syndrome for potential PDHC deficiency, especially in females.
authors.affiliation: Department of Pediatrics, School of Medicine, University of Tokushima, Tokushima, Japan.
authors.forename: E
authors.initials: E
authors.lastname: Naito
authors.forename: M
authors.initials: M
authors.lastname: Ito
authors.forename: I
authors.initials: I
authors.lastname: Yokota
authors.forename: T
authors.initials: T
authors.lastname: Saijo
authors.forename: S
authors.initials: S
authors.lastname: Chen
authors.forename: M
authors.initials: M
authors.lastname: Maehara
authors.forename: Y
authors.initials: Y
authors.lastname: Kuroda
mesh_terms: D019943:Amino Acid Substitution; D004252:DNA Mutational Analysis; D003999:Dichloroacetic Acid / Q000008:administration & dosage*; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007223:Infant; D019344:Lactic Acid / Q000097:blood / Q000134:cerebrospinal fluid; D030481:Pyruvate Dehydrogenase (Lipoamide); D011768:Pyruvate Dehydrogenase Complex / Q000235:genetics*; D015325:Pyruvate Dehydrogenase Complex Deficiency Disease / Q000188:drug therapy* / Q000503:physiopathology*; D012737:Sex Factors; D013036:Spasms, Infantile / Q000097:blood / Q000188:drug therapy* / Q000201:enzymology; D013831:Thiamine / Q000008:administration & dosage*
chemical_list: D011768:Pyruvate Dehydrogenase Complex; D019344:Lactic Acid; D003999:Dichloroacetic Acid; D030481:Pyruvate Dehydrogenase (Lipoamide); C065640:pyruvate dehydrogenase E1alpha subunit; D013831:Thiamine