Adrenoleukodystrophy: new approaches to a neurodegenerative disease

JAMA. 2005 Dec 28;294(24):3131-4. doi: 10.1001/jama.294.24.3131.


X-linked adrenoleukodystrophy (X-ALD), which was first described in 1923, was viewed until 1976 as a rare and inexorably fatal neurodegenerative disorder that affected boys. The genetic defect and biochemical abnormalities have now been defined. Ongoing research has resulted in new findings: (1) there is a wide range of phenotypic expression. At least half of patients with X-ALD are adults with somewhat milder manifestations, and women who are carriers may become symptomatic. X-ALD is often misdiagnosed as attention-deficit/hyperactivity disorder in boys and as multiple sclerosis in men and women, and is not an uncommon cause of Addison disease; (2) the incidence of X-ALD, estimated to be 1:17,000 in all ethnic groups, approximates that of phenylketonuria; (3) noninvasive and presymptomatic diagnosis and prenatal diagnosis are available; family screening and genetic counseling are key to disease prevention; and (4) new therapies, applied early, show promise. Neonatal screening is likely to become available, and a wider awareness of X-ALD and its various modes of presentation permit new proactive approaches to this distressing disorder.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adrenal Cortex Hormones / therapeutic use
  • Adrenoleukodystrophy* / diagnosis
  • Adrenoleukodystrophy* / genetics
  • Adrenoleukodystrophy* / physiopathology
  • Adrenoleukodystrophy* / therapy
  • Drug Combinations
  • Erucic Acids / therapeutic use
  • Fatty Acids / blood
  • Hematopoietic Stem Cell Transplantation
  • Hormone Replacement Therapy
  • Humans
  • Phenotype
  • Triolein / therapeutic use


  • Adrenal Cortex Hormones
  • Drug Combinations
  • Erucic Acids
  • Fatty Acids
  • Lorenzo's oil
  • Triolein