2. Academic Validation
  3. Hypertryptophanemia due to tryptophan 2,3-dioxygenase deficiency

Hypertryptophanemia due to tryptophan 2,3-dioxygenase deficiency

  • Mol Genet Metab. 2017 Apr;120(4):317-324. doi: 10.1016/j.ymgme.2017.02.009.
Patrick Ferreira 1,  Inchul Shin 2,  Iveta Sosova 3,  Kednerlin Dornevil 4,  Shailly Jain 5,  Deborah Dewey 6,  Fange Liu 4,  Aimin Liu 7
Affiliations

Affiliations

  • 1 Division of Medical Genetics, Alberta Children's Hospital, Calgary, AB, Canada. Electronic address: [email protected].
  • 2 Department of Chemistry, University of Texas at San Antonio, San Antonio, TX, USA.
  • 3 Department of Laboratory Medicine and Pathology, University of Alberta, Edmonton, AB, Canada.
  • 4 Department of Chemistry, University of Texas at San Antonio, San Antonio, TX, USA; Department of Chemistry, Georgia State University, Atlanta, GA, USA.
  • 5 Department of Medical Genetics, University of Alberta, Edmonton, AB, Canada.
  • 6 Department of Pediatrics, University of Calgary, Calgary, AB, Canada; Department of Community Health Sciences, University of Calgary, Calgary, AB, Canada.
  • 7 Department of Chemistry, University of Texas at San Antonio, San Antonio, TX, USA; Department of Chemistry, Georgia State University, Atlanta, GA, USA. Electronic address: [email protected].
PMID: 28285122 DOI: 10.1016/j.ymgme.2017.02.009
Abstract

In this report we describe the first human case of hypertryptophanemia confirmed to be due to tryptophan 2,3-dioxygenase deficiency. The underlying etiology was established by sequencing the TDO2 gene, in which there was compound heterozygosity for two rare variants: c.324G>C, p.Met108Ile and c.491dup, p.Ile165Aspfs*12. The pathogenicity of these variants was confirmed by molecular-level studies, which showed that c.491dup does not produce soluble protein and c.324G>C results in a catalytically less efficient Met108Ile Enzyme that is prone to proteolytic degradation. The biochemical phenotype of hypertryptophanemia and hyperserotoninemia does not appear to have significant clinical consequences.

Keywords

Hyperserotoninemia; Hypertryptophanemia; TDO2; Tryptophan 2,3-dioxygenase.

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