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Thiamine Responsive Pyruvate Dehydrogenase Complex Deficiency: A Potentially Treatable Cause of Leigh's Disease

Pyruvate dehydrogenase complex (PDHC) deficiency is a rare metabolic disorder that affects tissues with high energy demand such as the central nervous system. The clinico-radiological phenotype of Leigh's disease is one of its common presentations. We present a 9-month-old boy with rapidly prog...

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Autores principales: Jauhari, Prashant, Sankhyan, Naveen, Vyas, Sameer, Singhi, Pratibha
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Medknow Publications & Media Pvt Ltd 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5696666/
https://www.ncbi.nlm.nih.gov/pubmed/29204204
http://dx.doi.org/10.4103/jpn.JPN_191_16
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author Jauhari, Prashant
Sankhyan, Naveen
Vyas, Sameer
Singhi, Pratibha
author_facet Jauhari, Prashant
Sankhyan, Naveen
Vyas, Sameer
Singhi, Pratibha
author_sort Jauhari, Prashant
collection PubMed
description Pyruvate dehydrogenase complex (PDHC) deficiency is a rare metabolic disorder that affects tissues with high energy demand such as the central nervous system. The clinico-radiological phenotype of Leigh's disease is one of its common presentations. We present a 9-month-old boy with rapidly progressive infantile Leigh's disease. PDHA1 gene sequencing revealed a pathological homozygous missense mutation c.131A>G or p.H44R in exon 3 consistent with PDHC deficiency. H44R is among the five mutations (H44R, R88S, G89S, R263G, and V389fs) in E1α subunit that is thiamine-responsive. The child was initiated on thiamine, riboflavin, carnitine, coenzyme Q, and sodium benzoate supplementation. Mild recovery was noted at 6 months follow up as no further episodes of encephalopathy occurred. Thereafter, the child was treated with Ketogenic diet which resulted in increased levels of activity and alertness. Despite an improving course, the child had a sudden unexpected death at the age of 21 months.
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spelling pubmed-56966662017-12-04 Thiamine Responsive Pyruvate Dehydrogenase Complex Deficiency: A Potentially Treatable Cause of Leigh's Disease Jauhari, Prashant Sankhyan, Naveen Vyas, Sameer Singhi, Pratibha J Pediatr Neurosci Case Report Pyruvate dehydrogenase complex (PDHC) deficiency is a rare metabolic disorder that affects tissues with high energy demand such as the central nervous system. The clinico-radiological phenotype of Leigh's disease is one of its common presentations. We present a 9-month-old boy with rapidly progressive infantile Leigh's disease. PDHA1 gene sequencing revealed a pathological homozygous missense mutation c.131A>G or p.H44R in exon 3 consistent with PDHC deficiency. H44R is among the five mutations (H44R, R88S, G89S, R263G, and V389fs) in E1α subunit that is thiamine-responsive. The child was initiated on thiamine, riboflavin, carnitine, coenzyme Q, and sodium benzoate supplementation. Mild recovery was noted at 6 months follow up as no further episodes of encephalopathy occurred. Thereafter, the child was treated with Ketogenic diet which resulted in increased levels of activity and alertness. Despite an improving course, the child had a sudden unexpected death at the age of 21 months. Medknow Publications & Media Pvt Ltd 2017 /pmc/articles/PMC5696666/ /pubmed/29204204 http://dx.doi.org/10.4103/jpn.JPN_191_16 Text en Copyright: © 2017 Journal of Pediatric Neurosciences http://creativecommons.org/licenses/by-nc-sa/3.0 This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as the author is credited and the new creations are licensed under the identical terms.
spellingShingle Case Report
Jauhari, Prashant
Sankhyan, Naveen
Vyas, Sameer
Singhi, Pratibha
Thiamine Responsive Pyruvate Dehydrogenase Complex Deficiency: A Potentially Treatable Cause of Leigh's Disease
title Thiamine Responsive Pyruvate Dehydrogenase Complex Deficiency: A Potentially Treatable Cause of Leigh's Disease
title_full Thiamine Responsive Pyruvate Dehydrogenase Complex Deficiency: A Potentially Treatable Cause of Leigh's Disease
title_fullStr Thiamine Responsive Pyruvate Dehydrogenase Complex Deficiency: A Potentially Treatable Cause of Leigh's Disease
title_full_unstemmed Thiamine Responsive Pyruvate Dehydrogenase Complex Deficiency: A Potentially Treatable Cause of Leigh's Disease
title_short Thiamine Responsive Pyruvate Dehydrogenase Complex Deficiency: A Potentially Treatable Cause of Leigh's Disease
title_sort thiamine responsive pyruvate dehydrogenase complex deficiency: a potentially treatable cause of leigh's disease
topic Case Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5696666/
https://www.ncbi.nlm.nih.gov/pubmed/29204204
http://dx.doi.org/10.4103/jpn.JPN_191_16
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