Adrenoleukodystrophy

What is the definition of Adrenoleukodystrophy?

Adrenoleukodystrophy describes several closely related disorders that disrupt the breakdown of certain fats. These disorders are often passed down (inherited) in families.

What are the alternative names for Adrenoleukodystrophy?

X-linked Adrenoleukodystrophy; Adrenomyeloneuropathy; Childhood cerebral adrenoleukodystrophy; ALD; Schilder-Addison Complex

What are the causes for Adrenoleukodystrophy?

Adrenoleukodystrophy is usually passed down from parent to child as an X-linked genetic trait. It affects mostly males. Some women who are carriers can have milder forms of the disease. It affects about 1 in 20,000 people from all races.

The condition results in the buildup of very-long-chain fatty acids in the nervous system, adrenal gland, and testes. This disrupts normal activity in these parts of the body.

There are three major categories of disease:

• Childhood cerebral form -- appears in mid-childhood (at ages 4 to 8)
• Adrenomyelopathy -- occurs in men in their 20s or later in life
• Impaired adrenal gland function (called Addison disease or Addison-like phenotype) -- adrenal gland does not produce enough steroid hormones

What are the symptoms for Adrenoleukodystrophy?

Childhood cerebral type symptoms include:

• Changes in muscle tone, especially muscle spasms and uncontrolled movements
• Crossed eyes
• Handwriting that gets worse
• Difficulty at school
• Difficulty understanding what people are saying
• Hearing loss
• Hyperactivity
• Worsening nervous system damage, including coma, decreased fine motor control, and paralysis 
• Seizures
• Swallowing difficulties
• Visual impairment or blindness

Adrenomyelopathy symptoms include:

• Difficulty controlling urination
• Possible worsening muscle weakness or leg stiffness
• Problems with thinking speed and visual memory

Adrenal gland failure (Addison type) symptoms include:

• Coma
• Decreased appetite
• Increased skin color
• Loss of weight and muscle mass (wasting)
• Muscle weakness
• Vomiting

What are the current treatments for Adrenoleukodystrophy?

Adrenal dysfunction may be treated with steroids (such as cortisol) if the adrenal gland is not producing enough hormones.

A specific treatment for X-linked adrenoleukodystrophy is not available. A bone marrow transplant may stop worsening of the condition.

Supportive care and careful monitoring of impaired adrenal gland function may help in improving comfort and quality of life.

What are the support groups for Adrenoleukodystrophy?

The following resources can provide more information on adrenoleukodystrophy:

• National Organization for Rare Disease Disorders -- rarediseases.org/rare-diseases/adrenoleukodystrophy
• NIH/NLM Genetics Home Reference -- ghr.nlm.nih.gov/condition/x-linked-adrenoleukodystrophy

What is the outlook (prognosis) for Adrenoleukodystrophy?

The childhood form of X-linked adrenoleukodystrophy is a progressive disease. It leads to a long-term coma (vegetative state) about 2 years after nervous system symptoms develop. The child can live in this condition for as long as 10 years until death occurs.

The other forms of this disease are milder.

What are the possible complications for Adrenoleukodystrophy?

These complications can occur:

• Adrenal crisis
• Vegetative state

When should I contact a medical professional for Adrenoleukodystrophy?

Call your health care provider if:

• Your child develops symptoms of X-linked adrenoleukodystrophy
• Your child has X-linked adrenoleukodystrophy and is getting worse

How do I prevent Adrenoleukodystrophy?

Genetic counseling is recommended for couples with a family history of X-linked adrenoleukodystrophy. Mothers of affected sons have an 85% chance of being a carrier for this condition.

Prenatal diagnosis of X-linked adrenoleukodystrophy is also available. It is done by testing cells from chorionic villus sampling or amniocentesis. These tests look for either a known genetic change in the family or for very long chain fatty acid levels.

REFERENCES

James WD, Berger TG, Elston DM. Errors in metabolism. In: James WD, Berger TG, Elston DM, eds. Andrews' Diseases of the Skin: Clinical Dermatology. 12th ed. Philadelphia, PA: Elsevier; 2016:chap 26.

Lissauer T, Carroll W. Neurological disorders. In: Lissauer T, Carroll W, eds. Illustrated Textbook of Paediatrics. 5th ed. Philadelphia, PA: Elsevier; 2018:chap 29.

Stanley CA, Bennett MJ. Defects in metabolism of lipids. In: Kliegman RM, St. Geme JW, Blum NJ, Shah SS, Tasker RC, Wilson KM, eds. Nelson Textbook of Pediatrics. 21st ed. Philadelphia, PA: Elsevier; 2020:chap 104.

Vanderver A, Wolf NI. Genetic and metabolic disorders of the white matter. In: Swaiman KF, Ashwal S, Ferriero, et al, eds. Swaiman's Pediatric Neurology. 6th ed. Philadelphia, PA: Elsevier; 2017:chap 99.