{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,11]],"date-time":"2026-10-11T21:45:01Z","timestamp":1791755101866,"version":"4.3.4"},"reference-count":15,"publisher":"Georg Thieme Verlag KG","issue":"02","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Neuropediatrics"],"published-print":{"date-parts":[[2021,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>TPK deficiency due to TPK1 mutations is a rare neurodegenerative disorder, also known as thiamine metabolism dysfunction syndrome 5 (OMIM no.: 614458). Here, we report a new patient with compound heterozygous TPK1 mutations, of which one has not been described so far. The individual reported here suffered from acute onset encephalopathy, ataxia, muscle hypotonia, and regression of developmental milestones in early infancy, repeatedly triggered by febrile infections. Initiation of high-dose thiamine and magnesium supplementation led to a marked and sustained improvement of alertness, ataxia, and muscle tone within days. Contrary to the described natural history of patients with TPK deficiency, the disease course was favorable under thiamine treatment without deterioration or developmental regression during the follow-up period. TPK deficiency is a severe neurodegenerative disease. This case report demonstrates that this condition is potentially treatable. High-dose thiamine treatment should therefore be initiated immediately after diagnosis or even upon suspicion.<\/jats:p>","DOI":"10.1055\/s-0040-1715628","type":"journal-article","created":{"date-parts":[[2020,11,24]],"date-time":"2020-11-24T13:34:41Z","timestamp":1606224881000},"page":"126-132","source":"Crossref","is-referenced-by-count":13,"title":["Thiamine Pyrophosphokinase Deficiency due to Mutations in the TPK1 Gene: A Rare, Treatable Neurodegenerative Disorder"],"prefix":"10.1055","volume":"52","author":[{"given":"Christina T.","family":"R\u00fcsch","sequence":"additional","affiliation":[{"name":"Division of Pediatric Neurology and Children's Research Center, University Children's Hospital Zurich, Z\u00fcrich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saskia B.","family":"Wortmann","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics, Technische Universit\u00e4t M\u00fcnchen, M\u00fcnchen, Germany"},{"name":"Department of Pediatrics, Radboud Center for Mitochondrial Medicine, Amalia Children's Hospital, Radboudumc, Nijmegen, The Netherlands"},{"name":"Paracelcus Medical University (PMU), University Children's Hospital, Salzburg, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reka","family":"Kovacs-Nagy","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics, Technische Universit\u00e4t M\u00fcnchen, M\u00fcnchen, Germany"},{"name":"Department of Molecular Biology, Institute of Biochemistry and Molecular Biology, Semmelweis University, Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrice","family":"Grehten","sequence":"additional","affiliation":[{"name":"Department of Diagnostic Imaging and Children's Research Center, University Children's Hospital Zurich, Z\u00fcrich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johannes","family":"H\u00e4berle","sequence":"additional","affiliation":[{"name":"Division of Metabolism and Children's Research Center, University Children's Hospital Zurich, Z\u00fcrich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beatrice","family":"Latal","sequence":"additional","affiliation":[{"name":"Division of Child Department and Children's Research Center, University Children's Hospital Zurich, Z\u00fcrich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georg M.","family":"Stettner","sequence":"additional","affiliation":[{"name":"Division of Pediatric Neurology and Children's Research Center, University Children's Hospital Zurich, Z\u00fcrich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"194","published-online":{"date-parts":[[2020,11,23]]},"reference":[{"issue":"04","key":"ref1","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1002\/jimd.12125","article-title":"Genetic defects of thiamine transport and metabolism: A review of clinical phenotypes, genetics, and functional studies","volume":"42","author":"A Marc\u00e9-Grau","year":"2019","journal-title":"J Inherit Metab Dis"},{"issue":"04","key":"ref2","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1007\/s10545-014-9712-9","article-title":"Defects of thiamine transport and metabolism","volume":"37","author":"G Brown","year":"2014","journal-title":"J Inherit Metab Dis"},{"issue":"03","key":"ref3","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1002\/ana.24998","article-title":"Thiamine deficiency in childhood with attention to genetic causes: Survival and outcome predictors","volume":"82","author":"J D Ortigoza-Escobar","year":"2017","journal-title":"Ann Neurol"},{"issue":"06","key":"ref4","doi-asserted-by":"crossref","first-page":"806","DOI":"10.1016\/j.ajhg.2011.11.007","article-title":"Thiamine pyrophosphokinase deficiency in encephalopathic children with defects in the pyruvate oxidation pathway","volume":"89","author":"J A Mayr","year":"2011","journal-title":"Am J Hum Genet"},{"issue":"05","key":"ref5","doi-asserted-by":"crossref","first-page":"909","DOI":"10.1002\/jimd.12109","article-title":"Mitochondrial DNA mutation analysis from exome sequencing-A more holistic approach in diagnostics of suspected mitochondrial disease","volume":"42","author":"M Wagner","year":"2019","journal-title":"J Inherit Metab Dis"},{"issue":"07","key":"ref6","doi-asserted-by":"crossref","first-page":"755","DOI":"10.1080\/14737175.2016.1187562","article-title":"Treatment of genetic defects of thiamine transport and metabolism","volume":"16","author":"J D Ortigoza-Escobar","year":"2016","journal-title":"Expert Rev Neurother"},{"issue":"01","key":"ref7","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1016\/j.ymgmr.2013.12.007","article-title":"Thiamine pyrophosphokinase deficiency causes a Leigh Disease like phenotype in a sibling pair: identification through whole exome sequencing and management strategies","volume":"1","author":"J L Fraser","year":"2014","journal-title":"Mol Genet Metab Rep"},{"issue":"04","key":"ref8","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1016\/j.ymgme.2014.09.010","article-title":"Expanding the clinical and molecular spectrum of thiamine pyrophosphokinase deficiency: a treatable neurological disorder caused by TPK1 mutations","volume":"113","author":"S Banka","year":"2014","journal-title":"Mol Genet Metab"},{"issue":"08","key":"ref9","doi-asserted-by":"crossref","first-page":"870","DOI":"10.1212\/WNL.0000000000004270","article-title":"Thiamine-responsive disease due to mutation of tpk1: Importance of avoiding misdiagnosis","volume":"89","author":"F Invernizzi","year":"2017","journal-title":"Neurology"},{"key":"ref10","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1016\/j.jns.2017.02.063","article-title":"TPK1 mutation induced childhood onset idiopathic generalized dystonia: Report of a rare mutation and effect of deep brain stimulation","volume":"376","author":"A Mahajan","year":"2017","journal-title":"J Neurol Sci"},{"issue":"02","key":"ref11","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1007\/s00438-018-1517-3","article-title":"Reduced thiamine binding is a novel mechanism for TPK deficiency disorder","volume":"294","author":"W Huang","year":"2019","journal-title":"Mol Genet Genomics"},{"issue":"03","key":"ref12","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1515\/jpem-2018-0363","article-title":"Identification of two novel TPK1 gene mutations in a Chinese patient with thiamine pyrophosphokinase deficiency undergoing whole exome sequencing","volume":"32","author":"L Zhu","year":"2019","journal-title":"J Pediatr Endocrinol Metab"},{"issue":"07","key":"ref13","doi-asserted-by":"crossref","first-page":"991","DOI":"10.3390\/jcm8070991","article-title":"Utility of whole blood thiamine pyrophosphate evaluation in TPK1-related diseases","volume":"8","author":"E Bugiardini","year":"2019","journal-title":"J Clin Med"},{"key":"ref14","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.cca.2019.07.034","article-title":"Thiamine phosphokinase deficiency and mutation in TPK1 presenting as biotin responsive basal ganglia disease","volume":"499","author":"W L Nyhan","year":"2019","journal-title":"Clin Chim Acta"},{"issue":"02","key":"ref15","doi-asserted-by":"crossref","first-page":"e11","DOI":"10.1093\/brain\/aww303","article-title":"Treatable mitochondrial diseases: cofactor metabolism and beyond","volume":"140","author":"F Distelmaier","year":"2017","journal-title":"Brain"}],"container-title":["Neuropediatrics"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.thieme-connect.de\/products\/ejournals\/pdf\/10.1055\/s-0040-1715628.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,11,29]],"date-time":"2022-11-29T14:02:10Z","timestamp":1669730530000},"score":1,"resource":{"primary":{"URL":"http:\/\/www.thieme-connect.de\/DOI\/DOI?10.1055\/s-0040-1715628"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,11,23]]},"references-count":15,"journal-issue":{"issue":"02","published-online":{"date-parts":[[2021,3,19]]},"published-print":{"date-parts":[[2021,4]]}},"URL":"https:\/\/doi.org\/10.1055\/s-0040-1715628","relation":{},"ISSN":["0174-304X","1439-1899"],"issn-type":[{"value":"0174-304X","type":"print"},{"value":"1439-1899","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,11,23]]}}}