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Congenital lactic acidosis.

Y Kuroda1, E Naito, E Takeda

  • 1Department of Pediatrics, School of Medicine, University of Tokushima, Japan.

Enzyme
|January 1, 1987
PubMed
Summary
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A new assay using dichloroacetate (DCA) helps screen for pyruvate metabolism disorders. DCA also activates energy pathways and lowers lactate, suggesting its potential for treating congenital lactic acidosis.

Area of Science:

  • Biochemistry
  • Metabolic disorders
  • Clinical diagnostics

Background:

  • Congenital lactic acidosis is a group of rare metabolic disorders.
  • Pyruvate metabolism disorders, particularly pyruvate dehydrogenase (PDH) activation defects, are a known cause.
  • Accurate and sensitive diagnostic methods are crucial for early detection and treatment.

Purpose of the Study:

  • To develop a sensitive assay for screening pyruvate metabolism disorders.
  • To investigate the effect of dichloroacetate (DCA) on pyruvate metabolism and energy pathways.
  • To evaluate the therapeutic potential of DCA in congenital lactic acidosis.

Main Methods:

  • Development of a sensitive assay measuring (1-14C)-pyruvate decarboxylation rates in cultured skin fibroblasts.

Related Experiment Videos

  • Utilized dichloroacetate (DCA) as an activator in the assay.
  • Assessed the impact of DCA on PDH complex activity, the tricarboxylic acid cycle, and lactate levels in various tissues, including brain, blood, and cerebrospinal fluid.

    • Main Results:

    • Identified defects in pyruvate dehydrogenase (PDH) activation mechanism in 2 out of 10 patients with congenital lactic acidosis.
    • Demonstrated that DCA activates the PDH complex and the tricarboxylic acid cycle.
    • Observed a reduction in lactate levels in blood and cerebrospinal fluid following DCA administration.

    Conclusions:

    • The developed assay is effective for screening pyruvate metabolism disorders.
    • DCA shows promise as a therapeutic agent for chronic congenital lactic acidosis.
    • Early initiation of DCA therapy may be critical for effective treatment outcomes.