X-Linked Adrenoleukodystrophy

Genetics / Neurology

Overview

Definition

An X-linked peroxisomal disorder causing demyelination of the central nervous system and adrenal insufficiency due to accumulation of very long-chain fatty acids.

Epidemiology

Prevalence ~1 in 17,000 males.

Etiology & Risk Factors

  • ABCD1 gene mutation
  • Accumulation of VLCFAs in brain white matter and adrenal cortex

Clinical Symptoms

  • Behavioral changes and cognitive decline in boys
  • Vision and hearing loss
  • Spastic gait
  • Hyperpigmentation (signs of Addison's disease)

Clinical Approach

Diagnosis

  • Elevated plasma levels of Very Long-Chain Fatty Acids (VLCFAs)
  • Genetic testing for ABCD1 mutations
  • Brain MRI showing symmetric demyelination

Management

  • Corticosteroid replacement for adrenal insufficiency
  • Allogeneic stem cell transplant in early-stage cerebral disease
  • Lorenzo's oil (dietary therapy, controversial)

Complications

  • Vegetative state
  • Adrenal crisis
  • Severe spastic tetraparesis