AUTHOR=Choi Jae-Hwan , Kim Hyun Sung , Oh Eun Hye , Lee Jae Hyeok , Cheon Chong Kun 

TITLE=Cerebello-brainstem dominant form of X-linked adrenoleukodystrophy with intrafamilial phenotypic variability

JOURNAL=Frontiers in Neurology

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2022.999419

DOI=10.3389/fneur.2022.999419

ISSN=1664-2295

ABSTRACT=<sec><title>Objectives</title><p>This study aimed to describe the clinical and radiological characteristics of a cerebello-brainstem dominant form of X-linked adrenoleukodystrophy (X-ALD).</p></sec><sec><title>Methods</title><p>Three affected members from a family with cerebellar ataxia received full neurological, laboratory and radiological examinations. Genetic diagnoses were confirmed using whole-exome sequencing and protein structural modeling.</p></sec><sec><title>Results</title><p>All affected members presented with slurred speech, ataxia, and spasticity, but showed obvious differences in phenotypic severity and radiological findings. The levels of very long-chain fatty acids (VLCFA) were elevated in each member, while only one had adrenal dysfunction. Genetic analysis identified a hemizygous missense mutation (c.887A&gt;G, p.Tyr296Cys) of the ATP-binding cassette subfamily D member 1 gene (<italic>ABCD1</italic>) in all affected members, which is likely to destabilize the overall structure of the ABCD1 protein.</p></sec><sec><title>Conclusions</title><p>We report a cerebello-dominant form of X-ALD caused by a missense variant in <italic>ABCD1</italic>. This report highlights intrafamilial phenotypic variability in X-ALD.</p></sec>