{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T11:49:08Z","timestamp":1791978548616,"version":"4.4.0"},"reference-count":19,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2019,7,8]],"date-time":"2019-07-08T00:00:00Z","timestamp":1562544000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["G0601943"],"award-info":[{"award-number":["G0601943"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["MR\/S002065\/1"],"award-info":[{"award-number":["MR\/S002065\/1"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Seventh Framework Programme","award":["2012-305121"],"award-info":[{"award-number":["2012-305121"]}]},{"name":"E-Rare project GENOMIT","award":["FWF I 2741-B26"],"award-info":[{"award-number":["FWF I 2741-B26"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>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&gt;C (p. Leu142Phe) and c. 258+1G&gt;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.<\/jats:p>","DOI":"10.3390\/jcm8070991","type":"journal-article","created":{"date-parts":[[2019,7,8]],"date-time":"2019-07-08T11:02:37Z","timestamp":1562583757000},"page":"991","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Utility of Whole Blood Thiamine Pyrophosphate Evaluation in TPK1-Related Diseases"],"prefix":"10.3390","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9709-6699","authenticated-orcid":false,"given":"Enrico","family":"Bugiardini","sequence":"first","affiliation":[{"name":"MRC Centre for Neuromuscular Diseases, UCL Queen Square Institute of Neurology and National Hospital for Neurology and Neurosurgery, London WC1N 3BG, UK"},{"name":"Department of Neuromuscular Diseases, UCL Queen Square Institute of Neurology, London WC1N 3BG, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon","family":"Pope","sequence":"additional","affiliation":[{"name":"Neurometabolic Unit, National Hospital for Neurology and Neurosurgery, London WC1N 3BG, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4215-8258","authenticated-orcid":false,"given":"Ren\u00e9 G.","family":"Feichtinger","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University Hospital Salzburg, Paracelsus Medical University, 5020 Salzburg, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivia V.","family":"Poole","sequence":"additional","affiliation":[{"name":"MRC Centre for Neuromuscular Diseases, UCL Queen Square Institute of Neurology and National Hospital for Neurology and Neurosurgery, London WC1N 3BG, UK"},{"name":"Department of Neuromuscular Diseases, UCL Queen Square Institute of Neurology, London WC1N 3BG, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alan M.","family":"Pittman","sequence":"additional","affiliation":[{"name":"Department of Neuromuscular Diseases, UCL Queen Square Institute of Neurology, London WC1N 3BG, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cathy E.","family":"Woodward","sequence":"additional","affiliation":[{"name":"Neurogenetics Unit, National Hospital for Neurology and Neurosurgery, London WC1N 3BG, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon","family":"Heales","sequence":"additional","affiliation":[{"name":"Neurometabolic Unit, National Hospital for Neurology and Neurosurgery, London WC1N 3BG, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosaline","family":"Quinlivan","sequence":"additional","affiliation":[{"name":"MRC Centre for Neuromuscular Diseases, UCL Queen Square Institute of Neurology and National Hospital for Neurology and Neurosurgery, London WC1N 3BG, UK"},{"name":"Department of Neuromuscular Diseases, UCL Queen Square Institute of Neurology, London WC1N 3BG, UK"},{"name":"Dubowitz Neuromuscular Centre, Great Ormond Street Hospital, London WC1N 3JH, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henry","family":"Houlden","sequence":"additional","affiliation":[{"name":"MRC Centre for Neuromuscular Diseases, UCL Queen Square Institute of Neurology and National Hospital for Neurology and Neurosurgery, London WC1N 3BG, UK"},{"name":"Department of Neuromuscular Diseases, UCL Queen Square Institute of Neurology, London WC1N 3BG, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johannes A.","family":"Mayr","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University Hospital Salzburg, Paracelsus Medical University, 5020 Salzburg, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael 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