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Comparison Between Dichloroacetate and Phenylbutyrate Treatment for Pyruvate Dehydrogenase Deficiency

Pyruvate dehydrogenase (PDH) deficiency is caused by a number of pathogenic variants and the most common are found in the PDHA1 gene. The PDHA1 gene encodes one of the subunits of the PDH enzyme found in a carbohydrate metabolism pathway involved in energy production. Pathogenic variants of PDHA1 ge...

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Autores principales: Karissa, Patricia, Simpson, Timothy, Dawson, Simon P., Low, Teck Yew, Tay, Sook Hui, Nordin, Fatimah Diana Amin, Zain, Shamsul Mohd, Lee, Pey Yee, Pung, Yuh-Fen
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9302545/
https://www.ncbi.nlm.nih.gov/pubmed/35996497
http://dx.doi.org/10.3389/bjbs.2022.10382
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author Karissa, Patricia
Simpson, Timothy
Dawson, Simon P.
Low, Teck Yew
Tay, Sook Hui
Nordin, Fatimah Diana Amin
Zain, Shamsul Mohd
Lee, Pey Yee
Pung, Yuh-Fen
author_facet Karissa, Patricia
Simpson, Timothy
Dawson, Simon P.
Low, Teck Yew
Tay, Sook Hui
Nordin, Fatimah Diana Amin
Zain, Shamsul Mohd
Lee, Pey Yee
Pung, Yuh-Fen
author_sort Karissa, Patricia
collection PubMed
description Pyruvate dehydrogenase (PDH) deficiency is caused by a number of pathogenic variants and the most common are found in the PDHA1 gene. The PDHA1 gene encodes one of the subunits of the PDH enzyme found in a carbohydrate metabolism pathway involved in energy production. Pathogenic variants of PDHA1 gene usually impact the α-subunit of PDH causing energy reduction. It potentially leads to increased mortality in sufferers. Potential treatments for this disease include dichloroacetate and phenylbutyrate, previously used for other diseases such as cancer and maple syrup urine disease. However, not much is known about their efficacy in treating PDH deficiency. Effective treatment for PDH deficiency is crucial as carbohydrate is needed in a healthy diet and rice is the staple food for a large portion of the Asian population. This review analysed the efficacy of dichloroacetate and phenylbutyrate as potential treatments for PDH deficiency caused by PDHA1 pathogenic variants. Based on the findings of this review, dichloroacetate will have an effect on most PDHA1 pathogenic variant and can act as a temporary treatment to reduce the lactic acidosis, a common symptom of PDH deficiency. Phenylbutyrate can only be used on patients with certain pathogenic variants (p.P221L, p.R234G, p.G249R, p.R349C, p.R349H) on the PDH protein. It is hoped that the review would provide an insight into these treatments and improve the quality of lives for patients with PDH deficiency.
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spelling pubmed-93025452022-07-22 Comparison Between Dichloroacetate and Phenylbutyrate Treatment for Pyruvate Dehydrogenase Deficiency Karissa, Patricia Simpson, Timothy Dawson, Simon P. Low, Teck Yew Tay, Sook Hui Nordin, Fatimah Diana Amin Zain, Shamsul Mohd Lee, Pey Yee Pung, Yuh-Fen Br J Biomed Sci Health Archive Pyruvate dehydrogenase (PDH) deficiency is caused by a number of pathogenic variants and the most common are found in the PDHA1 gene. The PDHA1 gene encodes one of the subunits of the PDH enzyme found in a carbohydrate metabolism pathway involved in energy production. Pathogenic variants of PDHA1 gene usually impact the α-subunit of PDH causing energy reduction. It potentially leads to increased mortality in sufferers. Potential treatments for this disease include dichloroacetate and phenylbutyrate, previously used for other diseases such as cancer and maple syrup urine disease. However, not much is known about their efficacy in treating PDH deficiency. Effective treatment for PDH deficiency is crucial as carbohydrate is needed in a healthy diet and rice is the staple food for a large portion of the Asian population. This review analysed the efficacy of dichloroacetate and phenylbutyrate as potential treatments for PDH deficiency caused by PDHA1 pathogenic variants. Based on the findings of this review, dichloroacetate will have an effect on most PDHA1 pathogenic variant and can act as a temporary treatment to reduce the lactic acidosis, a common symptom of PDH deficiency. Phenylbutyrate can only be used on patients with certain pathogenic variants (p.P221L, p.R234G, p.G249R, p.R349C, p.R349H) on the PDH protein. It is hoped that the review would provide an insight into these treatments and improve the quality of lives for patients with PDH deficiency. Frontiers Media S.A. 2022-05-19 /pmc/articles/PMC9302545/ /pubmed/35996497 http://dx.doi.org/10.3389/bjbs.2022.10382 Text en Copyright © 2022 Karissa, Simpson, Dawson, Low, Tay, Nordin, Zain, Lee and Pung. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Health Archive
Karissa, Patricia
Simpson, Timothy
Dawson, Simon P.
Low, Teck Yew
Tay, Sook Hui
Nordin, Fatimah Diana Amin
Zain, Shamsul Mohd
Lee, Pey Yee
Pung, Yuh-Fen
Comparison Between Dichloroacetate and Phenylbutyrate Treatment for Pyruvate Dehydrogenase Deficiency
title Comparison Between Dichloroacetate and Phenylbutyrate Treatment for Pyruvate Dehydrogenase Deficiency
title_full Comparison Between Dichloroacetate and Phenylbutyrate Treatment for Pyruvate Dehydrogenase Deficiency
title_fullStr Comparison Between Dichloroacetate and Phenylbutyrate Treatment for Pyruvate Dehydrogenase Deficiency
title_full_unstemmed Comparison Between Dichloroacetate and Phenylbutyrate Treatment for Pyruvate Dehydrogenase Deficiency
title_short Comparison Between Dichloroacetate and Phenylbutyrate Treatment for Pyruvate Dehydrogenase Deficiency
title_sort comparison between dichloroacetate and phenylbutyrate treatment for pyruvate dehydrogenase deficiency
topic Health Archive
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9302545/
https://www.ncbi.nlm.nih.gov/pubmed/35996497
http://dx.doi.org/10.3389/bjbs.2022.10382
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