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.