Untargeted metabolomics identifies unique though benign biochemical changes in patients with pathogenic variants in UROC1

Urocanic aciduria is caused by a deficiency in the enzyme urocanase (E.C. 4.2.1.49) encoded by the gene UROC1. In the past, deficiency of urocanase has been associated with intellectual disability in a few case studies with some suggestion that the enzyme deficiency was the causative etiology. Here,...

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Main Authors:	Kevin E. Glinton, Harvey L. Levy, Adam D. Kennedy, Kirk L. Pappan, Sarah H. Elsea
Format:	Article
Language:	English
Published:	Elsevier 2019-03-01
Series:	Molecular Genetics and Metabolism Reports
Online Access:	http://www.sciencedirect.com/science/article/pii/S2214426918301125

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spelling	doaj-d383456f1d174c2d8e2911a232af14902020-11-24T21:05:59ZengElsevierMolecular Genetics and Metabolism Reports2214-42692019-03-01181418Untargeted metabolomics identifies unique though benign biochemical changes in patients with pathogenic variants in UROC1Kevin E. Glinton0Harvey L. Levy1Adam D. Kennedy2Kirk L. Pappan3Sarah H. Elsea4Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA; Corresponding author at: Department of Molecular and Human Genetics, Baylor College of Medicine, 6701 Fannin Street, Suite 1560, Houston, TX 77030, USA.Boston Children's Hospital, Harvard Medical School, Boston, MA, USAMetabolon, Inc., Morrisville, NC, USAMetabolon, Inc., Morrisville, NC, USADepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USAUrocanic aciduria is caused by a deficiency in the enzyme urocanase (E.C. 4.2.1.49) encoded by the gene UROC1. In the past, deficiency of urocanase has been associated with intellectual disability in a few case studies with some suggestion that the enzyme deficiency was the causative etiology. Here, we describe two phenotypically normal siblings with compound heterozygous pathogenic variants in UROC1 and characteristic biochemical evidence of urocanase deficiency collected utilizing untargeted metabolomic analysis. These findings suggest that urocanic aciduria may represent an otherwise benign biochemical phenotype and that those individuals with concurrent developmental delay should continue to be evaluated for other underlying causes for their symptoms. Keywords: UROC1, Urocanic aciduria, Untargeted metabolomics, Cis-urocanate, Trans-urocanate, Imidazole propionatehttp://www.sciencedirect.com/science/article/pii/S2214426918301125
collection	DOAJ
language	English
format	Article
sources	DOAJ
author	Kevin E. Glinton Harvey L. Levy Adam D. Kennedy Kirk L. Pappan Sarah H. Elsea
spellingShingle	Kevin E. Glinton Harvey L. Levy Adam D. Kennedy Kirk L. Pappan Sarah H. Elsea Untargeted metabolomics identifies unique though benign biochemical changes in patients with pathogenic variants in UROC1 Molecular Genetics and Metabolism Reports
author_facet	Kevin E. Glinton Harvey L. Levy Adam D. Kennedy Kirk L. Pappan Sarah H. Elsea
author_sort	Kevin E. Glinton
title	Untargeted metabolomics identifies unique though benign biochemical changes in patients with pathogenic variants in UROC1
title_short	Untargeted metabolomics identifies unique though benign biochemical changes in patients with pathogenic variants in UROC1
title_full	Untargeted metabolomics identifies unique though benign biochemical changes in patients with pathogenic variants in UROC1
title_fullStr	Untargeted metabolomics identifies unique though benign biochemical changes in patients with pathogenic variants in UROC1
title_full_unstemmed	Untargeted metabolomics identifies unique though benign biochemical changes in patients with pathogenic variants in UROC1
title_sort	untargeted metabolomics identifies unique though benign biochemical changes in patients with pathogenic variants in uroc1
publisher	Elsevier
series	Molecular Genetics and Metabolism Reports
issn	2214-4269
publishDate	2019-03-01
description	Urocanic aciduria is caused by a deficiency in the enzyme urocanase (E.C. 4.2.1.49) encoded by the gene UROC1. In the past, deficiency of urocanase has been associated with intellectual disability in a few case studies with some suggestion that the enzyme deficiency was the causative etiology. Here, we describe two phenotypically normal siblings with compound heterozygous pathogenic variants in UROC1 and characteristic biochemical evidence of urocanase deficiency collected utilizing untargeted metabolomic analysis. These findings suggest that urocanic aciduria may represent an otherwise benign biochemical phenotype and that those individuals with concurrent developmental delay should continue to be evaluated for other underlying causes for their symptoms. Keywords: UROC1, Urocanic aciduria, Untargeted metabolomics, Cis-urocanate, Trans-urocanate, Imidazole propionate
url	http://www.sciencedirect.com/science/article/pii/S2214426918301125
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Untargeted metabolomics identifies unique though benign biochemical changes in patients with pathogenic variants in UROC1

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