Disease spectrum in X-linked adrenoleukodystrophy (ALD)

Clinical syndrome	Age of presentation	Symptoms and signs	Diagnostic tests	Follow-up tests	Therapy
Male
Leukodystrophy	>2 years (peak 4 to 8); rare after 50 years	Asymptomatic to severely disabled, depending on degree of white matter lesions	MRI of brain (pathognomonic); VLCFA; ABCD1 sequencing	MRI of brain	HCT in eligible patients
Spinal cord disease and peripheral neuropathy	>20 years (but highly variable, can be much later)	Myelopathy with spasticity, sphincter dysfunction, and prominent dorsal column dysfunction	MRI of brain and spinal cord; VLCFA; ABCD1 sequencing		Supportive
Adrenal insufficiency	>1 year (85% before 18 years)	Hyperpigmentation, fatigue, malaise, orthostasis, adrenal crisis	ACTH stimulation test		Hormone replacement
Female
Spinal cord disease and peripheral neuropathy	>40 years (can be earlier or much later)	Myelopathy with spasticity, sphincter dysfunction, and prominent dorsal column dysfunction	VLCFA; ABCD1 sequencing		Supportive

Patients with ALD are asymptomatic at birth but develop symptoms during life. Virtually all male and female patients eventually develop spinal cord disease, though age of onset is highly variable. The lifetime prevalence of leukodystrophy is 60% in male patients. Adrenal insufficiency occurs in 85% of male patients before the age of 45. Leukodystrophy and adrenal insufficiency are exceedingly rare in female patients.

MRI: magnetic resonance imaging; VLCFA: very long chain fatty acids assay in plasma; HCT: hematopoietic stem cell transplantation; ACTH: adrenocorticotropic hormone.

Reference:

Moser HW, Raymond GV, Dubey P. Adrenoleukodystrophy: New approaches to a neurodegenerative disease. JAMA 2005; 294:3131.

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Disease spectrum in X-linked adrenoleukodystrophy (ALD)