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Variants associated with urea cycle disorders in Japanese patients: Nationwide study and literature review
Author(s) -
Kido Jun,
Matsumoto Shirou,
Sugawara Keishin,
Sawada Takaaki,
Nakamura Kimitoshi
Publication year - 2021
Publication title -
american journal of medical genetics part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.064
H-Index - 112
eISSN - 1552-4833
pISSN - 1552-4825
DOI - 10.1002/ajmg.a.62199
Subject(s) - hyperammonemia , argininosuccinate synthase , carbamoyl phosphate synthetase , ornithine transcarbamylase , argininosuccinate lyase , urea cycle , medicine , ornithine transcarbamylase deficiency , liver transplantation , pediatrics , transplantation , biology , gene , arginase , genetics , arginine , amino acid
Abstract Urea cycle disorders (UCDs) are inherited metabolic diseases that lead to hyperammonemia with variable clinical manifestations. Using data from a nationwide study, we investigated the onset time, gene variants, clinical manifestations, and treatment of patients with UCDs in Japan. Of the 229 patients with UCDs diagnosed and/or treated between January 2000 and March 2018, identified gene variants and clinical information were available for 102 patients, including 62 patients with ornithine transcarbamylase (OTC) deficiency, 18 patients with carbamoyl phosphate synthetase 1 (CPS1) deficiency, 16 patients with argininosuccinate synthetase (ASS) deficiency, and 6 patients with argininosuccinate lyase (ASL) deficiency. A total of 13, 10, 4, and 5 variants in the OTC , CPS1 , ASS , and ASL genes were respectively identified as novel variants, which were neither registered in ClinVar databases nor previously reported. The onset time and severity in patients with UCD could be predicted based on the identified gene variants in each patient from this nationwide study and previous studies. This genetic information may help in predicting the long‐term outcome and determining specific treatment strategies such as liver transplantation in patients with UCDs.