A Distinct Clinical Phenotype in Two Siblings with X-linked Adrenoleukodystrophy

Neuro Endocrinol Lett. 2019 Mar;40(1):36-40.


Objectives: X-linked adrenoleukodystrophy(X-ALD) is a rare X-linked recessive metabolic disorder. The mutations in the ATP Binding Cassette Subfamily D Member 1 (ABCD1) gene account for the underlying molecular mechanism. Herein, we present two siblings with X-ALD due to a missense, presumably identical, ABCD1 mutation, who had extremely distinct clinical phenotypes.

Material and methods: Patient 1 (6y/o) was admitted with primary adrenal insufficiency (PAI). His VLCFA analysis and cranial MRI suggested the diagnosis of X-ALD with no cranial involvement. Although the PAI was successfully managed using hydrocortisone replacement therapy, during follow-up he was admitted with the complaints of perception impairment, seizures, loss of vision and deafness suggesting cranial involvement which was not able to be recovered despite intensive supportive therapies; in the end patient died. Patient 2 (21y/o) had mild symptoms of PAI with no organ manifestation. He was undertaken to a molecular genetics analysis for ABCD1 gene due to history of his brother. His VLCFA analysis revealed mildly elevated C26, C22 and C26/C22 ratio suggesting ALD diagnosis. However, his cranial imaging and other results were within normal limits.

Conclusion: Two siblings with X-ALD due to presumably an identical, missense ABCD1 mutation and distinct clinical phenotype have confirmed the lack of phenotype-genotype correlation and proved the essential role of molecular genetics analysis in the early diagnosis. It is crucial to follow up for the development of cranial involvement and decide a bone marrow transplantation which is the only option that can prevent the progression of the disease, thus extend the lifespan.

Publication types

  • Case Reports

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily D, Member 1 / genetics*
  • Adrenoleukodystrophy / diagnosis*
  • Adrenoleukodystrophy / diagnostic imaging
  • Adrenoleukodystrophy / genetics
  • Brain / diagnostic imaging*
  • Child
  • Fatal Outcome
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Mutation, Missense*
  • Phenotype
  • Siblings
  • Young Adult


  • ATP Binding Cassette Transporter, Subfamily D, Member 1