A Case of Adrenomyeloneuropathy with Later Development of Cerebral Form Caused by a Hemizygous Splice-site Variant in ABCD1

Naoki Takegami; Takashi Matsukawa; Masashi Hamada; Shuichi Tanifuji; Takayuki Tamura; Nanaka Yamaguchi-Takegami; Hiroyuki Ishiura; Jun Mitsui; Kaori Sakuishi; Shoji Tsuji; Tatsushi Toda

doi:10.2169/internalmedicine.2240-23

This article has now been updated. Please use the final version.

A Case of Adrenomyeloneuropathy with Later Development of Cerebral Form Caused by a Hemizygous Splice-site Variant in ABCD1

Naoki Takegami, Takashi Matsukawa, Masashi Hamada, Shuichi Tanifuji, Takayuki Tamura, Nanaka Yamaguchi-Takegami, Hiroyuki Ishiura, Jun Mitsui, Kaori Sakuishi, Shoji Tsuji, Tatsushi Toda

Author information

Naoki Takegami
Department of Neurology, Graduate School of Medicine, The University of Tokyo, Japan
Takashi Matsukawa
Department of Neurology, Graduate School of Medicine, The University of Tokyo, Japan
Masashi Hamada
Department of Neurology, Graduate School of Medicine, The University of Tokyo, Japan
Shuichi Tanifuji
Department of Neurology, Graduate School of Medicine, The University of Tokyo, Japan
Takayuki Tamura
Department of Neurology, Graduate School of Medicine, The University of Tokyo, Japan
Nanaka Yamaguchi-Takegami
Department of Neurology, Graduate School of Medicine, The University of Tokyo, Japan
Hiroyuki Ishiura
Department of Neurology, Graduate School of Medicine, The University of Tokyo, Japan
Jun Mitsui
Department of Neurology, Graduate School of Medicine, The University of Tokyo, Japan
Department of Precision Medicine Neurology, Graduate School of Medicine, The University of Tokyo, Japan
Kaori Sakuishi
Department of Neurology, Graduate School of Medicine, The University of Tokyo, Japan
Department of Neurology, Teikyo University Chiba Medical Center, Japan
Shoji Tsuji
Department of Neurology, Graduate School of Medicine, The University of Tokyo, Japan
Institute of Medical Genomics, International University of Health and Welfare, Japan
Tatsushi Toda
Department of Neurology, Graduate School of Medicine, The University of Tokyo, Japan

Keywords: adrenomyeloneuropathy, adrenoleukodystrophy, ABCD1, RNA, nonsense-mediated mRNA decay

JOURNAL OPEN ACCESS Advance online publication

Article ID: 2240-23

DOI https://doi.org/10.2169/internalmedicine.2240-23

The final version of this article is now available: Vol. 63 (2024), No. 7 pp. 999-1004

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Abstract

Adrenomyeloneuropathy (AMN)/adrenoleukodystrophy (ALD) is an X-linked genetic disorder caused by pathogenic variants in ABCD1. We treated a 54-year-old man with slowly progressive spastic paraparesis with later development of the cerebral form. A pathogenic splice-site variant of ABCD1 (c.1489-1G>A, p. Val497Alafs*51) and elevated levels of very long-chain fatty acids were found, leading to the diagnosis of AMN. Detailed ABCD1 mRNA expression analyses revealed decreased levels of ABCD1 mRNA accompanied by deletion of the first 31 bp in exon 6. The altered mRNA transcriptional patterns associated with splice site variants are diverse and may provide important insights into ALD pathogenesis.

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