Adrenoleukodystrophy siblings with a novel ABCD1 missense variant presenting with phenotypic differences: a case report and literature review.

Hiroyuki Ishiura, Yuka Shibata, Masaaki Matsushima, Takashi Matsukawa, Shoji Tsuji, Ichiro Yabe

Journal: Journal of human genetics 2021;66(5):535-537

PMID: 33127985

Abstract

Adrenoleukodystrophy (ALD) is an X-linked disease that affects primarily the white matter of the central nervous system and adrenal cortex. A correlation between genotypes and phenotypes has not been observed. Here, we present two Japanese siblings with a novel missense variant (c.1887T > G) in the ABCD1 gene who presented with different clinical phenotypes, i.e., adolescent cerebral and cerebello-brainstem types. We also review the literature focusing on the variation in the clinical phenotypes within ALD families. In our review, 61.9% of sibling pairs presented with the same clinical type of ALD and 59.1% of sibling pairs presented with a similar age of onset. Conversely, 15.4% of sibling pairs had a similar age of onset, but different clinical types of ALD. To observe the correlation between genotypes and phenotypes, it is important to diagnose early and to accumulate reports describing age of onset, first onset symptom, and progression of the symptom.

Address: Division of Clinical Genetics, Hokkaido University Hospital, Sapporo, Japan.; Department of Neurology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Japan.; Department of Molecular Neurology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.; Department of Neurology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.; Institute of Medical Genomics, International University of Health and Welfare, Chiba, Japan.; Division of Clinical Genetics, Hokkaido University Hospital, Sapporo, Japan. [email protected].; Department of Neurology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Japan. [email protected].

DOI: 10.1038/s10038-020-00866-x

MeSH Terms: ATP Binding Cassette Transporter, Subfamily D, Member 1, Adrenoleukodystrophy, Age of Onset, Amino Acid Substitution, Brain Stem, Cerebellum, Cerebral Cortex, Fatal Outcome, Humans, Lipoma, Male, Memory Disorders, Mutation, Missense, Neuroimaging, Pedigree, Phenotype, Point Mutation, Siblings, Soft Tissue Neoplasms, Spinal Dysraphism, Strabismus, Young Adult