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

• Published in: Journal of human genetics Vol. 66; no. 5; pp. 535 - 537
• Main Authors: Shibata, Yuka, Matsushima, Masaaki, Matsukawa, Takashi, Ishiura, Hiroyuki, Tsuji, Shoji, Yabe, Ichiro
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 01-05-2021
• Subjects: Adrenal cortex; Adrenoleukodystrophy; Age; Brain stem; Case reports; Central nervous system; Genotypes; Literature reviews; Phenotypes; Phenotypic variations; Siblings; Substantia alba
• ISSN: 1434-5161; 1435-232X
• DOI: 10.1038/s10038-020-00866-x

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.