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Thiamine-responsive congenital lactic acidosis: clinical and biochemical studies

Mitsuo Toyoshima1, Akira Oka, Yoshiko Egi

  • 1Division of Child Neurology, Institute of Neurological Science, Faculty of Medicine, Tottori University, Yonago, Japan.

Pediatric Neurology
|August 10, 2005
PubMed

Insights

Thiamine-responsive congenital lactic acidosis in infants can impair multiple metabolic pathways despite normal pyruvate dehydrogenase complex activity. Early thiamine therapy is crucial to prevent brain damage.

Area of Science:

  • Biochemistry
  • Genetics
  • Pediatrics

Background:

  • Congenital lactic acidosis is a group of inherited metabolic disorders.
  • Thiamine-responsive congenital lactic acidosis (TR-CLA) presents with elevated lactate and pyruvate levels.
  • The specific metabolic defects in TR-CLA are not fully understood.

Observation:

  • Six infants with TR-CLA and normal in vitro pyruvate dehydrogenase complex activity were studied.
  • Elevated urinary excretion of alpha-ketoglutarate, alpha-ketoadipate, and branched-chain ketoacids was observed.
  • Transport systems (THTR-1, THTR-2) and thiamine pyrophosphokinase (hTPK1) showed no abnormalities.

Findings:

  • Functional impairment of multiple thiamine-dependent enzymes, including pyruvate dehydrogenase complex, alpha-ketoglutarate dehydrogenase complex, and branched-chain amino acid dehydrogenase, was indicated.
  • Despite normal activity of key enzymes in vitro, in vivo metabolic dysfunction was evident.
  • No genetic defects were found in thiamine transport or pyrophosphorylation.

Implications:

  • Early diagnosis and prompt thiamine administration are critical to prevent irreversible neurological damage in infants with TR-CLA.
  • Monitoring lactate and pyruvate levels can aid in optimizing thiamine dosage.
  • Further research into the precise mechanisms of thiamine metabolism in TR-CLA is warranted.

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