Hypertryptophanemia due to tryptophan 2,3-dioxygenase deficiency

Patrick Ferreira; Inchul Shin; Iveta Sosova; Kednerlin Dornevil; Shailly Jain; Deborah Dewey; Fange Liu; Aimin Liu

doi:10.1016/j.ymgme.2017.02.009

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. Epub 2017 Mar 1.

Authors

Patrick Ferreira¹, Inchul Shin², Iveta Sosova³, Kednerlin Dornevil⁴, Shailly Jain⁵, Deborah Dewey⁶, Fange Liu⁴, Aimin Liu⁷

Affiliations

¹ Division of Medical Genetics, Alberta Children's Hospital, Calgary, AB, Canada. Electronic address: patrick.ferreira@ahs.ca.
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: Feradical@utsa.edu.

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.

Publication types

Case Reports

MeSH terms

Amino Acid Metabolism, Inborn Errors / genetics*
Catalytic Domain
Female
Genetic Predisposition to Disease
HeLa Cells
Humans
Infant, Newborn
Mutation*
Protein Structure, Tertiary
Sequence Analysis, DNA
Tryptophan Oxygenase / chemistry
Tryptophan Oxygenase / genetics*

Hypertryptophanemia due to tryptophan 2,3-dioxygenase deficiency

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