X-Linked Adrenoleukodystrophy

KEY FACTS

Terminology

• Abbreviations

  • X-linked adrenoleukodystrophy (X-ALD)

  • Classic childhood ALD (CCALD)

• Inherited peroxisomal disorder

  • ABCD1 mutation → impaired β-oxidation of very-long-chain fatty acids (VLCFAs)

  • Accumulation of VLCFAs in white matter causes severe inflammatory demyelination

• Several clinical forms of ALD and related disorders

  • Classic X-ALD

    • –

      Severe form almost exclusively in boys 5-12 years old

  • At least 6 variants other than classic childhood X-ALD

    • –

      Presymptomatic X-ALD, adolescent ALD, adult ALD, adrenomyeloneuropathy (AMN), Addison only, symptomatic female carriers

  • AMN

    • –

      “Mild” adult (spinocerebellar) form, cerebral involvement in up to 50%

    • –

      X-ALD and AMN account for 80% of cases

Imaging

• 3 zones of myelin loss in CCALD

  • Innermost: Necrotic astrogliotic core

  • Intermediate: Enhancing active demyelination, inflammation

  • Peripheral: Advancing demyelination without inflammation

• Usually symmetrical, confluent, posterior involvement; rare frontal pattern (~ 10%)

Pathology

• Clinical heterogeneity attributed to specific mutations, modifying factors

• Phenotypic variability: CCALD, AMN → presymptomatic presentations even within same family

Clinical Issues

• X-ALD and variants = 1:16,800 North American births

• Common clinical features

  • Behavioral changes, learning disability

  • Blindness, quadriparesis

  • Seizures (progressive, generally late in course)

• Lorenzo oil delays symptoms in presymptomatic ALD

Diagnostic Checklist

• X-ALD presenting at atypical ages

  • Atypical appearances common

    • –

      Lacks enhancement, may have frontal (rather than posterior) “gradient”

• Always enhance unknown leukodystrophy

TERMINOLOGY

IMAGING