Neuropediatrics 2021; 52(02): 126-132
DOI: 10.1055/s-0040-1715628
Short Communication

Thiamine Pyrophosphokinase Deficiency due to Mutations in the TPK1 Gene: A Rare, Treatable Neurodegenerative Disorder

Christina T. Rüsch
1  Division of Pediatric Neurology and Children's Research Center, University Children's Hospital Zurich, Zürich, Switzerland
,
Saskia B. Wortmann
2  Institute of Human Genetics, Technische Universität München, München, Germany
3  Department of Pediatrics, Radboud Center for Mitochondrial Medicine, Amalia Children's Hospital, Radboudumc, Nijmegen, The Netherlands
4  Paracelcus Medical University (PMU), University Children's Hospital, Salzburg, Austria
,
Reka Kovacs-Nagy
2  Institute of Human Genetics, Technische Universität München, München, Germany
5  Department of Molecular Biology, Institute of Biochemistry and Molecular Biology, Semmelweis University, Budapest, Hungary
,
Patrice Grehten
6  Department of Diagnostic Imaging and Children's Research Center, University Children's Hospital Zurich, Zürich, Switzerland
,
Johannes Häberle
7  Division of Metabolism and Children's Research Center, University Children's Hospital Zurich, Zürich, Switzerland
,
Beatrice Latal
8  Division of Child Department and Children's Research Center, University Children's Hospital Zurich, Zürich, Switzerland
,
Georg M. Stettner
1  Division of Pediatric Neurology and Children's Research Center, University Children's Hospital Zurich, Zürich, Switzerland
› Author Affiliations

Abstract

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.

Disclosure

All coauthors do not report conflicts of interest.




Publication History

Received: 02 April 2020

Accepted: 25 June 2020

Publication Date:
23 November 2020 (online)

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