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.
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.