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Utility of Whole Blood Thiamine Pyrophosphate Evaluation in TPK1-Related Diseases

TPK1 mutations are a rare, but potentially treatable, cause of thiamine deficiency. Diagnosis is challenging given the phenotypic overlap that exists with other metabolic and neurological disorders. We report a case of TPK1-related disease presenting with Leigh-like syndrome and review the diagnosti...

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Autores principales: Bugiardini, Enrico, Pope, Simon, Feichtinger, René G., Poole, Olivia V., Pittman, Alan M., Woodward, Cathy E., Heales, Simon, Quinlivan, Rosaline, Houlden, Henry, Mayr, Johannes A., Hanna, Michael G., Pitceathly, Robert D.S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6679130/
https://www.ncbi.nlm.nih.gov/pubmed/31288420
http://dx.doi.org/10.3390/jcm8070991
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author Bugiardini, Enrico
Pope, Simon
Feichtinger, René G.
Poole, Olivia V.
Pittman, Alan M.
Woodward, Cathy E.
Heales, Simon
Quinlivan, Rosaline
Houlden, Henry
Mayr, Johannes A.
Hanna, Michael G.
Pitceathly, Robert D.S.
author_facet Bugiardini, Enrico
Pope, Simon
Feichtinger, René G.
Poole, Olivia V.
Pittman, Alan M.
Woodward, Cathy E.
Heales, Simon
Quinlivan, Rosaline
Houlden, Henry
Mayr, Johannes A.
Hanna, Michael G.
Pitceathly, Robert D.S.
author_sort Bugiardini, Enrico
collection PubMed
description TPK1 mutations are a rare, but potentially treatable, cause of thiamine deficiency. Diagnosis is challenging given the phenotypic overlap that exists with other metabolic and neurological disorders. We report a case of TPK1-related disease presenting with Leigh-like syndrome and review the diagnostic utility of thiamine pyrophosphate (TPP) blood measurement. The proband, a 35-year-old male, presented at four months of age with recurrent episodes of post-infectious encephalopathy. He subsequently developed epilepsy, learning difficulties, sensorineural hearing loss, spasticity, and dysphagia. There was a positive family history for Leigh syndrome in an older brother. Plasma lactate was elevated (3.51 mmol/L) and brain MRI showed bilateral basal ganglia hyperintensities, indicative of Leigh syndrome. Histochemical and spectrophotometric analysis of mitochondrial respiratory chain complexes I, II+III, and IV was normal. Genetic analysis of muscle mitochondrial DNA was negative. Whole exome sequencing of the proband confirmed compound heterozygous variants in TPK1: c. 426G>C (p. Leu142Phe) and c. 258+1G>A (p.?). Blood TPP levels were reduced, providing functional evidence for the deleterious effects of the variants. We highlight the clinical and bioinformatics challenges to diagnosing rare genetic disorders and the continued utility of biochemical analyses, despite major advances in DNA sequencing technology, when investigating novel, potentially disease-causing, genetic variants. Blood TPP measurement represents a fast and cost-effective diagnostic tool in TPK1-related diseases.
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spelling pubmed-66791302019-08-19 Utility of Whole Blood Thiamine Pyrophosphate Evaluation in TPK1-Related Diseases Bugiardini, Enrico Pope, Simon Feichtinger, René G. Poole, Olivia V. Pittman, Alan M. Woodward, Cathy E. Heales, Simon Quinlivan, Rosaline Houlden, Henry Mayr, Johannes A. Hanna, Michael G. Pitceathly, Robert D.S. J Clin Med Case Report TPK1 mutations are a rare, but potentially treatable, cause of thiamine deficiency. Diagnosis is challenging given the phenotypic overlap that exists with other metabolic and neurological disorders. We report a case of TPK1-related disease presenting with Leigh-like syndrome and review the diagnostic utility of thiamine pyrophosphate (TPP) blood measurement. The proband, a 35-year-old male, presented at four months of age with recurrent episodes of post-infectious encephalopathy. He subsequently developed epilepsy, learning difficulties, sensorineural hearing loss, spasticity, and dysphagia. There was a positive family history for Leigh syndrome in an older brother. Plasma lactate was elevated (3.51 mmol/L) and brain MRI showed bilateral basal ganglia hyperintensities, indicative of Leigh syndrome. Histochemical and spectrophotometric analysis of mitochondrial respiratory chain complexes I, II+III, and IV was normal. Genetic analysis of muscle mitochondrial DNA was negative. Whole exome sequencing of the proband confirmed compound heterozygous variants in TPK1: c. 426G>C (p. Leu142Phe) and c. 258+1G>A (p.?). Blood TPP levels were reduced, providing functional evidence for the deleterious effects of the variants. We highlight the clinical and bioinformatics challenges to diagnosing rare genetic disorders and the continued utility of biochemical analyses, despite major advances in DNA sequencing technology, when investigating novel, potentially disease-causing, genetic variants. Blood TPP measurement represents a fast and cost-effective diagnostic tool in TPK1-related diseases. MDPI 2019-07-08 /pmc/articles/PMC6679130/ /pubmed/31288420 http://dx.doi.org/10.3390/jcm8070991 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Case Report
Bugiardini, Enrico
Pope, Simon
Feichtinger, René G.
Poole, Olivia V.
Pittman, Alan M.
Woodward, Cathy E.
Heales, Simon
Quinlivan, Rosaline
Houlden, Henry
Mayr, Johannes A.
Hanna, Michael G.
Pitceathly, Robert D.S.
Utility of Whole Blood Thiamine Pyrophosphate Evaluation in TPK1-Related Diseases
title Utility of Whole Blood Thiamine Pyrophosphate Evaluation in TPK1-Related Diseases
title_full Utility of Whole Blood Thiamine Pyrophosphate Evaluation in TPK1-Related Diseases
title_fullStr Utility of Whole Blood Thiamine Pyrophosphate Evaluation in TPK1-Related Diseases
title_full_unstemmed Utility of Whole Blood Thiamine Pyrophosphate Evaluation in TPK1-Related Diseases
title_short Utility of Whole Blood Thiamine Pyrophosphate Evaluation in TPK1-Related Diseases
title_sort utility of whole blood thiamine pyrophosphate evaluation in tpk1-related diseases
topic Case Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6679130/
https://www.ncbi.nlm.nih.gov/pubmed/31288420
http://dx.doi.org/10.3390/jcm8070991
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