- this is an X-linked recessive disorder resulting in the accumulation of long-chain fatty acid esters of cholesterol.
- patients have adrenal insufficiency.
Adrenoleukodystrophy (also known as X-linked adrenoleukodystrophy) is a genetic disorder of peroxisomal fatty acid beta oxidation caused by mutations in the ABCD1 gene
- this gene is usually passed by the mother to her offspring but can arise de novo
- the X-linked inheritance pattern means that males are more severely affected as they only have a single X chromosome. Female carriers tend to avoid the more severe clinical manifestations but can become symptomatic later in life.
There are a range of different clinical phenotypes:
- childhood cerebral adrenoleukodystrophy in affected males is associated with rapidly progressive demyelination in the brain
- typically presents during childhood with attention deficit and hyperactivity, visual and hearing impairment and co-ordination problems and can rapidly progress to severe disability and death without treatment
- other phenotypes include Addison’s disease and adrenomyeloneuropathy
- Addison’s disease in affected males is characterised by unexplained vomiting, weakness, dehydration, dizziness and sweating which can lead to coma
- adrenomyeloneuropathy is characterised by neurodegeneration of the spinal cord and peripheral nerves resulting in progressive stiffness and weakness in the legs, sphincter dysfunction, impotence and sensory loss in the lower limbs in affected males as adults, with similar symptoms in adult female carriers
- adrenoleukodystrophy phenotypes develop over time and are often preceded by adrenal insufficiency in males 
The only currently available standard therapy for adrenoleukodystrophy includes cortisol for individuals with adrenal insufficiency and haematopoietic stem cell transplant in boys with childhood cerebral adrenoleukodystrophy which can be effective if performed early in the evolution of the disease 
- currently no interventions that can slow or prevent the onset of adrenomyeloneuropathy for which only symptomatic support is available 
- though asymptomatic at birth, boys need to be routinely monitored with a combination of adrenal function, to detect incipient adrenal insufficiency, and brain MRI to identify early evidence of cerebral demyelination with a view to referral for consideration of haematopoietic stem cell transplant .
- Solutions for Public Health. Newborn screening for adrenoleukodystrophy: pilot assessment of topic submission. January 2017.
- Kemper AR, Brosco J, Comeau AM, Green NS, Grosse SD, Jones E, et al. Newborn screening for X-linked adrenoleukodystrophy: evidence summary and advisory committee recommendation. Genet Med. 2017, 19(1):121-6.
- Turk BR, Moser AB, Fatemi A. Therapeutic strategies in adrenoleukodystrophy. Wiener Medizinische Wochenschrift. 2017, 167(9):219-26.
- Brosco J, Comeau AM, Green NS, Grosse S, Kwon J, Prosser LA, et al. Newborn Screening for X-Linked Adrenoleukodystrophy (X-ALD): A Systematic Review of Evidence Final Report (v5. 01). 2015
Last edited 09/2020 and last reviewed 09/2020