Abstract

Volume.127 Number.11

Original article : Case report

A Case of a Boy with Gyrate Atrophy of the Choroid and Retina Caused by Compound Heterozygous Mutations in Ornithine Aminotransferase (OAT) Gene
Yuta Nakano1, Sayuri Yasuda1,2, Kei Mizobuchi3, Maiko Ikeda4, Takashi Hamajima4, Shinji Ueno2,5, Koji M. Nishiguchi2, Takaaki Hayashi3,6
1 Department of Ophthalmology, Aichi Children's Health and Medical Center
2 Department of Ophthalmology, Nagoya University Graduate School of Medicine
3 Department of Ophthalmology, The Jikei University School of Medicine
4 Department of Endocrinology and Metabolism, Aichi Children's Health and Medical Center
5 Department of Ophthalmology, Hirosaki University Graduate School of Medicine
6 Department of Ophthalmology, The Jikei University School of Medicine, Katsushika Medical Center

Purpose: Gyrate atrophy of the choroid and retina (GACR) is an autosomal recessive inherited congenital metabolic disorder rarely seen in the Japanese population. This disorder is characterized by hyperornithinemia caused by decreased activity of vitamin B6 (VitB6)-dependent ornithine aminotransferase (OAT), resulting in progressive chorioretinal degeneration. Here we report the case of a patient with GACR along with an investigation of previously reported Japanese GACR cases identified genetically.
Case: A 3-year-old boy was referred to our clinic for divergent strabismus. He had difficulty seeing at night for some time, but there was no obvious fundus abnormality. Further, the patient was followed up. Fundus examination at 6 years of age revealed a characteristic gyrus-like chorioretinal atrophy on the temporal side of the peripheral retina of both eyes. Moreover, full-field electroretinography revealed that both rod and cone system responses were absent. Hyperornithinemia was detected and GACR was strongly suspected; further, the administration of VitB6 was started. With this therapy, plasma ornithine levels did not decrease; however, after combining a low-protein diet with the therapy, these levels decreased. Eventually, reduced ornithine levels were maintained via protein restriction with essential amino acid administration and VitB6 administration. Whole-exome sequencing revealed compound heterozygous mutations (p.Arg271Lys and p. Arg426Ter) in OAT gene. Fundus examination at the age of 8 years revealed that the area of chorioretinal atrophy was clearly extended.
Conclusions: In the present case, the decreased plasma ornithine levels were maintained by the combination of low-protein diet and VitB6 administration, but the area of chorioretinal atrophy progressively extended. This report summarized OAT mutations in 13 previously reported Japanese GACR cases, including the present case, and found that the p. Arg426Ter mutation was very common (7 of 26 [27%] alleles).
Nippon Ganka Gakkai Zasshi (J Jpn Ophthalmol Soc) 127: 1069-1080, 2023.

Key words
Gyrate atrophy of the choroid and retina (GACR), Ornithine aminotransferase (OAT) gene, Whole exome sequencing, Vitamin B6, Low protein diet
Reprint requests to
Takaaki Hayashi, M. D.　Department of Ophthalmology, The Jikei University School of Medicine, Katsushika Medical Center. 6-41-2 Aoto, Katsushika-ku, Tokyo 125-8506, Japan
Received: 5 March 2023. Accepted in revised form: 23 May 2023.
Nihon Ganka Gakkai Zasshi 127: 1069-1080,2023