HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

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.
AuthorsMitsuo Toyoshima, Akira Oka, Yoshiko Egi, Toshiyuki Yamamoto, Mari Onozuka, Kazuto Nosaka, Etsuo Naito, Kazuo Yamada
JournalPediatric neurology (Pediatr Neurol) Vol. 33 Issue 2 Pg. 98-104 (Aug 2005) ISSN: 0887-8994 [Print] United States
PMID16087053 (Publication Type: Case Reports, Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Membrane Transport Proteins
  • SLC19A2 protein, human
  • SLC19A3 protein, human
  • Ketoglutarate Dehydrogenase Complex
  • Thiamin Pyrophosphokinase
  • Thiamine
Topics
  • Acidosis, Lactic (congenital, drug therapy, genetics, metabolism)
  • Brain (enzymology, pathology)
  • Female
  • Genotype
  • Humans
  • Infant
  • Infant, Newborn
  • Ketoglutarate Dehydrogenase Complex (metabolism)
  • Magnetic Resonance Imaging
  • Male
  • Membrane Transport Proteins (genetics)
  • Thiamin Pyrophosphokinase (genetics, metabolism)
  • Thiamine (administration & dosage, pharmacokinetics)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: