title: Thiamine-responsive congenital lactic acidosis: clinical and biochemical studies.
abstract: We studied six infants with thiamine-responsive congenital lactic acidosis and normal pyruvate dehydrogenase complex activity in vitro, through clinical and biochemical analysis. In addition to elevated lactate and pyruvate levels, the data revealed increased urinary excretion of alpha-ketoglutarate, alpha-ketoadipate, and branched chain ketoacids, indicating functional impairment of thiamine-requiring enzymes, such as pyruvate dehydrogenase complex, alpha-ketoglutarate dehydrogenase complex, alpha-ketoadipate dehydrogenase, and branched chain amino acid dehydrogenase. The metabolism of thiamine has not been investigated in patients with thiamine-responsive congenital lactic acidosis. We evaluated two specific transport systems, THTR-1 (SLC19A2) and THTR-2 (SLC19A3), and a pyrophosphorylating enzyme of thiamine, thiamine pyrophosphokinase (hTPK 1), in addition to pyruvate dehydrogenase complex and alpha-ketoglutarate dehydrogenase complex activity; no abnormality was found. Although the clinical features of thiamine-responsive congenital lactic acidosis are heterogeneous and clinical responses to thiamine administration vary, we emphasize the importance of early diagnosis and initiation of thiamine therapy before the occurrence of permanent brain damage. Careful monitoring of lactate and pyruvate would be useful in determining thiamine dosage.
authors.affiliation: Division of Child Neurology, Institute of Neurological Science, Faculty of Medicine, Tottori University, Yonago, Japan.
authors.forename: Mitsuo
authors.initials: M
authors.lastname: Toyoshima
authors.forename: Akira
authors.initials: A
authors.lastname: Oka
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Egi
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Yamamoto
authors.forename: Mari
authors.initials: M
authors.lastname: Onozuka
authors.forename: Kazuto
authors.initials: K
authors.lastname: Nosaka
authors.forename: Etsuo
authors.initials: E
authors.lastname: Naito
authors.forename: Kazuo
authors.initials: K
authors.lastname: Yamada
mesh_terms: D000140:Acidosis, Lactic / Q000151:congenital / Q000188:drug therapy* / Q000235:genetics* / Q000378:metabolism; D001921:Brain / Q000201:enzymology* / Q000473:pathology; D005260:Female; D005838:Genotype; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007655:Ketoglutarate Dehydrogenase Complex / Q000378:metabolism; D008279:Magnetic Resonance Imaging; D008297:Male; D026901:Membrane Transport Proteins / Q000235:genetics; D013836:Thiamin Pyrophosphokinase / Q000235:genetics / Q000378:metabolism; D013831:Thiamine / Q000008:administration & dosage* / Q000493:pharmacokinetics
chemical_list: D026901:Membrane Transport Proteins; C120043:SLC19A2 protein, human; C492291:SLC19A3 protein, human; D007655:Ketoglutarate Dehydrogenase Complex; D013836:Thiamin Pyrophosphokinase; D013831:Thiamine