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

Neuropediatrics. 2021 Apr;52(2):126-132. doi: 10.1055/s-0040-1715628. Epub 2020 Nov 23.


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.

Publication types

  • Case Reports

MeSH terms

  • Child
  • Dietary Supplements
  • Humans
  • Magnesium / administration & dosage
  • Neurodegenerative Diseases / diet therapy*
  • Neurodegenerative Diseases / physiopathology*
  • Rare Diseases
  • Thiamin Pyrophosphokinase / deficiency*
  • Thiamin Pyrophosphokinase / genetics*
  • Thiamine / administration & dosage
  • Thiamine / pharmacology*
  • Vitamin B Complex / administration & dosage
  • Vitamin B Complex / pharmacology*


  • Vitamin B Complex
  • Thiamin Pyrophosphokinase
  • Magnesium
  • Thiamine