X-linked adrenoleukodystrophy

Alternative names	X-ALD
About the condition	X-ALD is a peroxisomal disorder of complex lipid transport. This results in accumulation of very long chain fatty acids, which is toxic to the adrenals, spinal cord and brain. X-ALD has variable presentations within individuals, even within the same family, and typically have a progressive course. Males are more severely affected and common presentation types include neurodegeneration (acute cerebral ALD), late-onset adrenomyeloneuropathy (AMN), and/or adrenal insufficiency. Females may present much later in life with spinal involvement
Inheritance	X-linked
Year screening started in WA	2026
Incidence in Australia	1:15,000
Defect	X-ALDis caused by mutations in the ABCD1 gene, which encodes for ALD protein that transports very longchain fatty acids across the peroxisomal membrane for breakdown and processing.
Clinical Features	Muscle weakness and difficulty in walking. Urinary and bowel incontinence. Adrenal insufficiency (Addison’s disease). Behavioural and learning difficulties. Nausea, fatigue and vomiting. Blindness. Progressive neurodegeneration and premature death.
Determinantson bloodspot screening	Bloodspot C26:0 lysophosphotidylcholine (C26:0-LPC)
Diagnostic tests	Plasma C26:0-LPC and very long chain fatty acids ABCD1 gene analysis
Management	Clinical and neurological examination Monitoring of adrenal function. Adrenocorticoid hormone replacement therapy. Surveillance by brain MRI. Bone marrow or stem cell transplant for cerebral X-ALD. Supportive management.
Screening issues	Screening for X-ALD using C26:0-LPC may very rarely detect peroxisomal biogenesis disorder.