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

OBJECTIVES: This study aimed to describe the clinical and radiological characteristics of a cerebello-brainstem dominant form of X-linked adrenoleukodystrophy (X-ALD). METHODS: 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. RESULTS: 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>G, p.Tyr296Cys) of the ATP-binding cassette subfamily D member 1 gene (ABCD1) in all affected members, which is likely to destabilize the overall structure of the ABCD1 protein. CONCLUSIONS: We report a cerebello-dominant form of X-ALD caused by a missense variant in ABCD1. This report highlights intrafamilial phenotypic variability in X-ALD.