Adrenoleukodystrophy

Introduction
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By Raphael Schiffmann MD

Adrenoleukodystrophy is also known as or subsumes Addison-Schilder disease, Encephalitis periaxialis diffusa, Siewerling-Creutzfeldt disease, Sudanophilic leukodystrophy, and Schilder disease. -ed.

X-linked adrenoleukodystrophy (X-ALD) is the most common leukodystrophy with an estimated incidence of 1:17,000. Both men and women may be affected. Plasma very long chain fatty acid concentrations are already elevated at birth. VLCFA screening of at-risk relatives and of patients with idiopathic Addison disease permits diagnosis prior to neurologic involvement. Three therapies are in current use: adrenal steroid replacement, preventive therapy with Lorenzo Oil for asymptomatic patients with normal MRI, and hematopoietic stem cell transplantation for patients with early cerebral involvement. The latter, however, does not correct the adrenal insufficiency. There is growing evidence that ABCD1 dysfunction affects mitochondrial function. Newborn screening for this disorder is being developed.

Key points

  • X-linked adrenoleukodystrophy is the most common leukodystrophy.
  • It combines a genetic defect with an inflammatory brain reaction and adrenal insufficiency.
  • The frequency of symptomatic heterozygote women increases sharply with age.
  • If initiated very early in the disease process, X-linked adrenoleukodystrophy can be effectively treated using hematopoietic stem cell transplantation.
  • Initial success in gene therapy using ex-vivo gene transfer has recently been described.

In This Article

Introduction
Historical note and nomenclature
Clinical manifestations
Clinical vignette
Etiology
Pathogenesis and pathophysiology
Epidemiology
Prevention
Differential diagnosis
Diagnostic workup
Prognosis and complications
Management
Pregnancy
Anesthesia
References cited
Contributors