Current status of surviving patients with arginase 1 deficiency in Japan

Jun Kido; Shirou Matsumoto; Eiko Takeshita; Chiemi Hayasaka; Keitaro Yamada; Jiro Kagawa; Yoko Nakajima; Tetsuya Ito; Hiroyuki Iijima; Fumio Endo; Kimitoshi Nakamura

doi:10.1016/j.ymgmr.2021.100805

Current status of surviving patients with arginase 1 deficiency in Japan

Mol Genet Metab Rep. 2021 Oct 1:29:100805. doi: 10.1016/j.ymgmr.2021.100805. eCollection 2021 Dec.

Authors

Affiliations

¹ Department of Pediatrics, Faculty of Life Sciences, Kumamoto University, Kumamoto City, Kumamoto, Japan.
² Department of Pediatrics, Yanagawa Institute for Developmental Disabilities, International University of Health and Welfare, Yanagawa City, Fukuoka, Japan.
³ Haruhi Children's Clinic, Kounan City, Aichi, Japan.
⁴ Department of Pediatric Neurology, Aichi Developmental Disability Center Central Hospital, Kasugai City, Aichi, Japan.
⁵ Department of Pediatrics, Fujieda Municipal General Hospital, Fujieda City, Shizuoka, Japan.
⁶ Department of Pediatrics, Fujita Health University School of Medicine, Toyoake City, Aichi, Japan.
⁷ Department of General Pediatrics & Interdisciplinary Medicine, National Center for Child Health and Development, Tokyo, Japan.

Abstract

Arginase 1 (ARG1) deficiency is a rare urea cycle disorder (UCD), with an estimated frequency of 1 per 2,200,000 births in Japan. Patients with ARG1 deficiency develop symptoms in late infancy or pre-school age with progressive neurological manifestations and sometimes present with severe hepatic disease. We previously investigated the status of UCDs in Japan; however, only one patient was identified as having ARG1 deficiency. Therefore, we aimed to investigate the current status of patients with ARG1 deficiency in 2018-2021 because almost 10 years have passed since the previous study. We present the disease history, clinical outcome, and treatment of five surviving patients with ARG1 deficiency and discuss the features of ARG1 deficiency in Japan. We found that clinicians often face difficulty in diagnosing ARG1 deficiency at the early stage of onset because of interpatient variability in onset time and clinical manifestations. Blood L-arginine and guanidino compounds were considered to be the major factors causing adverse neurodevelopmental outcomes. Therefore, early detection and intervention of ARG1 deficiency is essential for improved neurodevelopmental outcomes. Liver transplantation has been considered an effective treatment option that can dramatically improve the quality of life of patients, prior to the neurological manifestation of symptoms caused by ARG1 deficiency.

Keywords: Arginase 1 deficiency; CT, Computed tomography; Cholestasis; Epilepsy; GAA, Guanidino acetate; HPT, Hepaplastin test; Hyperargininemia; LT, Liver transplant; Liver transplantation; NBS, Newborn screening; UCD, Urea cycle disorder; WAIS, Wechsler Adult Intelligence Scale; WISC, Wechsler Intelligence Scale for Children.