Adrenoleukodystrophy siblings with a novel ABCD1 missense variant presenting with phenotypic differences: a case report and literature review

J Hum Genet. 2021 May;66(5):535-537. doi: 10.1038/s10038-020-00866-x. Epub 2020 Oct 30.


Adrenoleukodystrophy (ALD) is an X-linked disease that affects primarily the white matter of the central nervous system and adrenal cortex. A correlation between genotypes and phenotypes has not been observed. Here, we present two Japanese siblings with a novel missense variant (c.1887T > G) in the ABCD1 gene who presented with different clinical phenotypes, i.e., adolescent cerebral and cerebello-brainstem types. We also review the literature focusing on the variation in the clinical phenotypes within ALD families. In our review, 61.9% of sibling pairs presented with the same clinical type of ALD and 59.1% of sibling pairs presented with a similar age of onset. Conversely, 15.4% of sibling pairs had a similar age of onset, but different clinical types of ALD. To observe the correlation between genotypes and phenotypes, it is important to diagnose early and to accumulate reports describing age of onset, first onset symptom, and progression of the symptom.

Publication types

  • Case Reports
  • Comparative Study
  • Review

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily D, Member 1 / genetics*
  • Adrenoleukodystrophy / classification
  • Adrenoleukodystrophy / complications
  • Adrenoleukodystrophy / genetics*
  • Adrenoleukodystrophy / pathology
  • Age of Onset*
  • Amino Acid Substitution*
  • Brain Stem / diagnostic imaging
  • Brain Stem / pathology
  • Cerebellum / diagnostic imaging
  • Cerebellum / pathology
  • Cerebral Cortex / diagnostic imaging
  • Cerebral Cortex / pathology
  • Fatal Outcome
  • Humans
  • Lipoma / complications
  • Male
  • Memory Disorders / genetics
  • Mutation, Missense*
  • Neuroimaging
  • Pedigree
  • Phenotype
  • Point Mutation*
  • Siblings
  • Soft Tissue Neoplasms / complications
  • Spinal Dysraphism / complications
  • Strabismus / genetics
  • Young Adult


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