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Comparison Between Dichloroacetate and Phenylbutyrate Treatment for Pyruvate Dehydrogenase Deficiency

Patricia Karissa1, Timothy Simpson2, Simon P Dawson2

  • 1Division of Biomedical Science, Faculty of Science and Engineering, University of Nottingham Malaysia, Semenyih, Malaysia.

British Journal of Biomedical Science
|August 23, 2022
PubMed

Insights

Pyruvate dehydrogenase (PDH) deficiency, often caused by PDHA1 gene variants, can be managed with dichloroacetate or phenylbutyrate. Dichloroacetate offers broad efficacy for reducing lactic acidosis, while phenylbutyrate is effective for specific PDHA1 variants.

Area of Science:

  • Biochemistry
  • Genetics
  • Metabolic Disorders

Background:

  • Pyruvate dehydrogenase (PDH) deficiency is a serious condition resulting from pathogenic variants, most commonly in the PDHA1 gene.
  • This deficiency disrupts carbohydrate metabolism and energy production, potentially leading to increased mortality.
  • Effective treatments are vital, especially for populations relying on carbohydrates like rice.

Purpose of the Study:

  • To review the efficacy of dichloroacetate and phenylbutyrate as potential treatments for PDH deficiency.
  • To analyze treatment effectiveness based on specific PDHA1 pathogenic variants.
  • To provide insights for improving patient quality of life.

Main Methods:

  • Literature review of existing studies on dichloroacetate and phenylbutyrate for PDH deficiency.
  • Analysis of treatment efficacy correlated with specific PDHA1 gene variants.
  • Evaluation of symptom management, particularly lactic acidosis.

Main Results:

  • Dichloroacetate demonstrates efficacy against most PDHA1 variants, serving as a temporary treatment for lactic acidosis.
  • Phenylbutyrate's effectiveness is limited to patients with specific PDHA1 variants (p.P221L, p.R234G, p.G249R, p.R349C, p.R349H).

Conclusions:

  • Dichloroacetate and phenylbutyrate show potential in managing PDH deficiency, with varying efficacy based on genetic variants.
  • Targeted application of these treatments can help alleviate symptoms like lactic acidosis.
  • Further insights into these therapies may significantly improve the quality of life for individuals with PDH deficiency.

Keywords:
E1aPDHA1inborn error of metabolismlactic acidosismitochondrial disease

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