Triosephosphate Isomerase Deficiency: E105D Mutation in Unrelated Patients and Review of the Literature

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Selamioǧlu A., Karaca M., Balcl M. C., Körbeyli H. K., Durmuş A., Ylldlz E. P., ...More

Molecular Syndromology, 2023 (SCI-Expanded) identifier

  • Publication Type: Article / Article
  • Publication Date: 2023
  • Doi Number: 10.1159/000528192
  • Journal Name: Molecular Syndromology
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, EMBASE
  • Keywords: Haemolytic anaemia, Neurodegeneration, Propionyl carnitine, Triosephosphate isomerase deficiency
  • Istanbul University Affiliated: Yes


© 2023 The Author(s). Published by S. Karger AG, Basel.Introduction: Chronic haemolytic anaemia, increased susceptibility to infections, cardiomyopathy, neurodegeneration, and death in early childhood are the clinical findings of triosephosphate isomerase (TPI) deficiency, which is an ultra-rare disorder. The clinical and laboratory findings and the outcomes of 2 patients with TPI deficiency are reported, with a review of cases reported in the literature. Case Presentation: Two unrelated patients with haemolytic anaemia and neurologic findings who were diagnosed as having TPI deficiency are presented. Neonatal onset of initial symptoms was observed in both patients, and the age at diagnosis was around 2 years. The patients had increased susceptibility to infections and respiratory failure, but cardiac symptoms were not remarkable. Screening for inborn errors of metabolism revealed a previously unreported metabolic alteration determined using tandem mass spectrometry in acylcarnitine analysis, causing elevated propionyl carnitine levels in both patients. The patients had p.E105D (c.315G>C) homozygous mutations in the TPI1 gene. Although severely disabled, both patients are alive at the ages of 7 and 9 years. Discussion: For better management, it is important to investigate the genetic aetiology in patients with haemolytic anaemia with or without neurologic symptoms who do not have a definitive diagnosis. The differential diagnosis of elevated propionyl carnitine levels using tandem mass spectrometry screening should also include TPI deficiency.