Adrenoleukodystrophy - neuroendocrine pathogenesis and redefinition of natural history

Nat Rev Endocrinol. 2016 Oct;12(10):606-15. doi: 10.1038/nrendo.2016.90. Epub 2016 Jun 17.


X-Linked adrenoleukodystrophy (ALD) is a peroxisomal metabolic disorder with a highly complex clinical presentation. ALD is caused by mutations in the ABCD1 gene, which leads to the accumulation of very long-chain fatty acids in plasma and tissues. Virtually all men with ALD develop adrenal insufficiency and myelopathy. Approximately 60% of men develop progressive cerebral white matter lesions (known as cerebral ALD). However, one cannot identify these individuals until the early changes are seen using brain imaging. Women with ALD also develop myelopathy, but generally at a later age than men and adrenal insufficiency or cerebral ALD are very rare. Owing to the multisystem symptomatology of the disease, patients can be assessed by the paediatrician, general practitioner, endocrinologist or a neurologist. This Review describes current knowledge on the clinical presentation, diagnosis and treatment of ALD, and highlights gaps in our knowledge of the natural history of the disease owing to an absence of large-scale prospective cohort studies. Such studies are necessary for the identification of new prognostic biomarkers to improve care for patients with ALD, which is particularly relevant now that newborn screening for ALD is being introduced.

Publication types

  • Review

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily D, Member 1
  • ATP-Binding Cassette Transporters / genetics
  • ATP-Binding Cassette Transporters / metabolism*
  • Adrenal Insufficiency / metabolism
  • Adrenoleukodystrophy / diagnosis
  • Adrenoleukodystrophy / drug therapy
  • Adrenoleukodystrophy / genetics
  • Adrenoleukodystrophy / metabolism*
  • Brain / diagnostic imaging
  • Disease Progression
  • Fatty Acids / metabolism*
  • Female
  • Glucocorticoids / therapeutic use
  • Hormone Replacement Therapy
  • Humans
  • Leukoencephalopathies / diagnostic imaging
  • Leukoencephalopathies / metabolism
  • Male
  • Peripheral Nervous System Diseases / metabolism
  • Spinal Cord Diseases / metabolism


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