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Adrenoleukodystrophy

Adrenoleukodystrophy is a genetic condition that damages the myelin sheath that covers nerve cells in the brain and spinal cord

Prevalence

1 / 17 000

1 - 15,000

US Estimated

1 - 15,000

Europe Estimated

Age of Onset

Childhood

ICD-10

E71.52

Inheritance Pattern

Autosomal dominant

Autosomal recessive

Mitochondrial/Multigenic

X-linked dominant

X-linked recessive

Rare View

A genetic disorder affecting the metabolism of very long-chain fatty acids, leading to progressive damage to the myelin sheath in the nervous system and adrenal gland dysfunction. It primarily affects males and can present in childhood or adulthood.

5 Facts you should know

FACT

1

Long chain fatty acid buildup causes damage to the myelin sheath of the nerves of the brain, resulting in seizures and hyperactivity

FACT

2

The most severely affected tissues are the myelin in the central nervous system, the adrenal cortex, and the Leydig cells in the testes

FACT

3

Approximately two-thirds of ALD patients will present with the childhood cerebral form of the disease, which is the most severe form

FACT

4

Initial symptoms in boys affected with the childhood cerebral form of ALD include emotional instability, hyperactivity, and disruptive behavior at school

FACT

5

The severe form is characterized by normal development in early childhood, followed by rapid degeneration to a vegetative state

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Adrenoleukodystrophy is also known as...

Adrenoleukodystrophy is also known as:

  • X-linked adrenoleukodystrophy
  • X-ALD
  • Childhood cerebral ALD (severe form)

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Common signs & symptoms

Endocrine

  • Fatigue
  • Weight loss
  • Hyperpigmentation
  • Hypoglycemia

Adult form (AMN)

  • Progressive spastic paraparesis
  • Gait abnormalities
  • Peripheral neuropathy

Neurologic

  • Behavioral changes
  • Cognitive decline
  • Loss of vision or hearing
  • Seizures
  • Progressive motor dysfunction

Current treatments

Adrenal hormone replacement when adrenal insufficiency present

For early active cerebral ALD

Allogeneic HSCT can arrest progression when performed early 

Gene therapy

SKYSONA (elivaldogene autotemcel) is FDA-indicated for boys 4–17 with early active cerebral ALD without a suitable matched donor

Supportive multidisciplinary care for AMN/neurologic disability

References:

Moser HW, Smith KD, Watkins PA, Powers J, Moser AB. X-linked adrenoleukodystrophy. <i>In: GeneReviews®.</i> University of Washington, Seattle; updated 2022. — Comprehensive overview of genetics, clinical phenotypes, diagnosis, and management. Engelen M, Kemp S, de Visser M, et al. X-linked adrenoleukodystrophy (X-ALD): clinical presentation and guidelines for diagnosis, follow-up and management. <i>Orphanet J Rare Dis.</i> 2012;7:51. doi:10.1186/1750-1172-7-51 Moser HW, Mahmood A, Raymond GV. X-linked adrenoleukodystrophy. <i>Nat Clin Pract Neurol.</i> 2007;3(3):140–151. doi:10.1038/ncpneuro0421 Mallack EJ, Turk BR, Yan H, et al. MRI surveillance of boys with X-linked adrenoleukodystrophy identified by newborn screening. <i>Neurology.</i> 2021;97(5):e413–e423. doi:10.1212/WNL.0000000000012319 Eichler F, Duncan C, Musolino PL, et al. Hematopoietic stem-cell gene therapy for cerebral adrenoleukodystrophy. <i>N Engl J Med.</i> 2017;377(17):1630–1638. doi:10.1056/NEJMoa1700554

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