Unmasking adrenoleukodystrophy in a cohort of cerebellar ataxia

PLoS One. 2017 May 8;12(5):e0177296. doi: 10.1371/journal.pone.0177296. eCollection 2017.


Adrenoleukodystrophy (ALD) is a rare and progressive neurogenetic disease that may manifest disparate symptoms. The present study aims at investigating the role of ataxic variant of ALD (AVALD) in patients with adult-onset cerebellar ataxia, as well as characterizing their clinical features that distinguish AVALD from other cerebellar ataxias. Mutations in the ATP binding cassette subfamily D member 1 gene (ABCD1) were ascertained in 516 unrelated patients with ataxia. The patients were categorized into three groups: molecularly unassigned hereditary ataxia (n = 118), sporadic ataxia with autonomic dysfunctions (n = 296), and sporadic ataxia without autonomic dysfunctions (n = 102). Brain MRIs were scrutinized for white matter hyperintensity (WMH) in the parieto-occipital lobes, frontal lobes, corticospinal tracts, pons, middle cerebellar peduncles and cerebellar hemispheres. Two ABCD1 mutations (p.S108L and p.P623fs) previously linked to cerebral ALD and adrenomyeloneuropathy but not AVALD were identified. ALD accounts for 0.85% (1/118) of the patients with molecularly unassigned hereditary ataxia and 0.34% (1/296) of the patients with sporadic ataxia with autonomic dysfunctions. WMH in the corticospinal tracts and WMH in the cerebellar hemispheres were strongly associated with AVALD rather than other ataxias. To conclude, ALD accounts for approximately 0.39% (2/516) of adult-onset cerebellar ataxias. This study expands the mutational spectrum of AVALD and underscores the importance of considering ALD as a potential etiology of cerebellar ataxia.

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily D, Member 1
  • ATP-Binding Cassette Transporters / genetics
  • Adrenoleukodystrophy / complications
  • Adrenoleukodystrophy / diagnosis*
  • Adrenoleukodystrophy / genetics
  • Adult
  • Cerebellar Ataxia / complications*
  • Cohort Studies
  • Female
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Mutation
  • Pedigree
  • Young Adult


  • ABCD1 protein, human
  • ATP Binding Cassette Transporter, Subfamily D, Member 1
  • ATP-Binding Cassette Transporters

Grants and funding

The research was supported by grants from the Ministry of Science & Technology, Taiwan, ROC (NSC102-2628-B-075-006-MY3, NSC103-2314-B-75-076-MY3 and MOST 103-2314-B-010-049-MY3, MOST 104-2314-B-075-045-MY4), the Brain Research Center, National Yang-Ming University (104AC-B19), the High-Throughput Genome Analysis Core Facility and Bioinformatics Consortium of Taiwan of the National Core Facility Program for Biotechnology, Taiwan (NSC 101-2319-B-010-001), and Taipei Veterans General Hospital (V103C-109, V104C-061, V104C-079, V104E9-006, V105C-118 and V105C-048), as well as research funds supported by the Taiwan Ataxia Association and the Hsu Tsung Pei Medical Research Fund.