Dataset Information

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

ABSTRACT:

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.

SUBMITTER: Choi JH

PROVIDER: S-EPMC9682283 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Publications

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

Choi Jae-Hwan JH Kim Hyun Sung HS Oh Eun Hye EH Lee Jae Hyeok JH Cheon Chong Kun CK

Frontiers in neurology 20221109

<h4>Objectives</h4>This study aimed to describe the clinical and radiological characteristics of a cerebello-brainstem dominant form of X-linked adrenoleukodystrophy (X-ALD).<h4>Methods</h4>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.<h4>Results</h4>All affected members presented with slurred speech, ataxia, and spasti ...[more]

PMID: 36438947

Similar Datasets

Project description:X-linked adrenoleukodystrophy (X-ALD) is the most common peroxisomal disorder and is caused by ABCD1 mutations. A cerebello-brainstem dominant form that mainly involves the cerebellum and brainstem is summarized in a review of the literature, with autopsy-confirmed cases exceedingly rare. We report a 69-year-old White man who was diagnosed with this rare disorder and describe neuropathologic, ultrastructural and genetic analyses. He did not have adrenal insufficiency or a family history of X-ALD or Addison's disease. His initial symptom was temporary loss of eyesight at age 34 years. His major symptoms were chronic and progressive gait disorder, weakness in his lower extremities and spasticity, as well as autonomic failure and cerebellar ataxia suggesting possible multiple system atrophy (MSA). He also had seizures, hearing loss and sensory disturbances. His brain MRI showed no obvious atrophy or significant white matter pathology in cerebrum, brainstem or cerebellum. He died at age 69 years with a diagnosis of MSA. Microscopic analysis showed mild, patchy myelin rarefaction with perivascular clusters of PAS-positive, CD68-positive macrophages in the white matter most prominent in the cerebellum and occipital lobe, but also affecting the optic tract and internal capsule. Electron microscopy of cerebellar white matter showed cleft-like trilamellar cytoplasmic inclusions in macrophages typical of X-ALD, which prompted genetic analysis that revealed a novel ABCD1 mutation, p.R163G. Given the relatively mild pathological findings and long disease duration, it is likely that the observed pathology was the result of a slow and indolent disease process. We described a patient who had sporadic cerebello-brainstem dominant form of X-ALD with long clinical course, mild pathological findings, and an ABCD1 p.R163G substitution. We also review a total of 34 cases of adult-onset cerebello-brainstem dominant form of X-ALD. Although rare, X-ALD should be considered in the differential diagnosis of MSA.

Dataset Information

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

Objectives

Methods

Results

Conclusions

Publications

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

Similar Datasets

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