title: Hypertryptophanemia due to tryptophan 2,3-dioxygenase deficiency.
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.
authors.affiliation: Division of Medical Genetics, Alberta Children's Hospital, Calgary, AB, Canada. Electronic address: patrick.ferreira@ahs.ca.
authors.forename: Patrick
authors.initials: P
authors.lastname: Ferreira
authors.affiliation: Department of Chemistry, University of Texas at San Antonio, San Antonio, TX, USA.
authors.forename: Inchul
authors.initials: I
authors.lastname: Shin
authors.affiliation: Department of Laboratory Medicine and Pathology, University of Alberta, Edmonton, AB, Canada.
authors.forename: Iveta
authors.initials: I
authors.lastname: Sosova
authors.affiliation: Department of Chemistry, University of Texas at San Antonio, San Antonio, TX, USA; Department of Chemistry, Georgia State University, Atlanta, GA, USA.
authors.forename: Kednerlin
authors.initials: K
authors.lastname: Dornevil
authors.affiliation: Department of Medical Genetics, University of Alberta, Edmonton, AB, Canada.
authors.forename: Shailly
authors.initials: S
authors.lastname: Jain
authors.affiliation: Department of Pediatrics, University of Calgary, Calgary, AB, Canada; Department of Community Health Sciences, University of Calgary, Calgary, AB, Canada.
authors.forename: Deborah
authors.initials: D
authors.lastname: Dewey
authors.affiliation: Department of Chemistry, University of Texas at San Antonio, San Antonio, TX, USA; Department of Chemistry, Georgia State University, Atlanta, GA, USA.
authors.forename: Fange
authors.initials: F
authors.lastname: Liu
authors.affiliation: 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.
authors.forename: Aimin
authors.initials: A
authors.lastname: Liu
mesh_terms: D000592:Amino Acid Metabolism, Inborn Errors / Q000235:genetics*; D020134:Catalytic Domain; D005260:Female; D020022:Genetic Predisposition to Disease; D006367:HeLa Cells; D006801:Humans; D007231:Infant, Newborn; D009154:Mutation; D017434:Protein Structure, Tertiary; D017422:Sequence Analysis, DNA; D014366:Tryptophan Oxygenase / Q000737:chemistry / Q000235:genetics*
chemical_list: D014366:Tryptophan Oxygenase
keywords: Hyperserotoninemia; Hypertryptophanemia; TDO2; Tryptophan 2,3-dioxygenase