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adrenoleukodystrophy

  • Adrenoleukodystrophy (ALD) is a rare, genetic, X-linked metabolic disorder caused by mutations in the ABCD1 gene that result in a deficiency in a peroxisomal protein called adrenoleukodystrophy protein (ALDP). This leads to the accumulation of very–long chain fatty acids (VLCFA) in various parts of the body, including the adrenal cortex and white matter of the brain and spinal cord, leading to a range of symptoms.
    • Males who inherit the ALD mutation will typically develop one or more of three sets of ALD symptoms. These are: primary adrenal insufficiency (where the body doesn’t make enough of certain key hormones), a progressive nervous system disorder called adrenomyeloneuropathy, and a severe, rapidly progressive degenerative brain disease called cerebral ALD (CALD).
  • CALD involves a progressive destruction of myelin, the protective sheath of the nerve cells in the brain that are responsible for thinking and muscle control. Symptoms usually occur in early childhood and progress rapidly if the disease is left untreated, leading to severe loss of neurologic function and, ultimately, death.
    • Currently, there is no way to predict which boys with ALD will go on to develop CALD. Boys with CALD may present with learning disabilities and behavioral problems that are often misdiagnosed as attention deficit hyperactivity disorder (ADHD), which may cause delays in accurate diagnosis.
  • Early diagnosis of CALD requires both early diagnosis of ALD and monitoring for the development of brain changes suggestive of CALD.
    • Newborn screening can be used to identify suspected ALD and is an important tool to increase the likelihood of timely diagnosis.
    • The early stages of CALD can be detected by brain MRI in boys with known ALD, even when they don’t have any noticeable symptoms. Therefore, it is recommended that all boys diagnosed with ALD who are aged 3 to 12 years be monitored every 6 months with MRI to detect early signs of brain involvement.1
  • There is currently no treatment approved for CALD. The only therapeutic intervention currently available to CALD patients is allogeneic stem cell transplantation (allo-HSCT, also known as BMT). In patients treated with allo‑HSCT, a beneficial effect on symptoms and long-term survival has been reported.
    • When allo-HSCT is performed in patients with MRI findings but without obvious symptoms, overall survival may be as high as 89% (95% CI, 70% to 96%) at 5 years after transplant, with complications such as infection, graft-versus-host disease (GVHD), and graft failure as causes of death.2
    • The safety of allo-HSCT is generally better if cells from a well-matched, related, donor are available. Unfortunately, it is common for boys with CALD not to have such a donor available.

You can find more information about BMT or ALD by visiting patient resources.

  1. Engelen M, Kemp S, de Visser M, et al. X-linked adrenoleukodystrophy (X-ALD): clinical presentation and guidelines for diagnosis, follow-up and management. Orphanet J Rare Dis. 2012;7:51.
  2. Miller WP, Rothman SM, Nascene D, et al. Outcomes after allogeneic hematopoietic cell transplantation for childhood cerebral adrenoleukodystrophy: the largest single-institution cohort report. Blood. 2011;118(7):1971-1978.