Adrenoleukodystrophy

Answer 1

Definition

Adrenoleukodystrophy describes several closely related inherited disorders that disrupt the breakdown (metabolism) of certain fats (very-long-chain fatty acids).

Alternative Names

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

Causes, incidence, and risk factors

Adrenoleukodystrophy is passed down from parents to their children as an X-linked genetic trait. It therefore affects mostly males, although some women who are carriers can have milder forms of the disease. It affects approximately 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, which disrupts normal activity. There are three major categories of disease:

• Childhood cerebral form -- appears in mid-childhood (at ages 4 - 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

Symptoms

Childhood cerebral type:

• Changes in muscle tone, especially muscle spasms and spasticity
• Crossed eyes(strabismus)
• Decreased understanding of verbal communication (aphasia)
• Deterioration of handwriting
• Difficulty at school
• Difficulty understanding spoken material
• Hearing loss
• Hyperactivity
• Worsening nervous system deterioration
  • Coma
  • Decreased fine motor control
  • Paralysis
• Seizures
• Swallowing difficulties
• Visual impairment or blindness

Adrenomyelopathy:

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

Adrenal gland failure (Addison type):

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

Signs and tests

• Blood levels
• Chromosome study to look for changes (mutations) in the ABCD1 gene
• MRI of the head

Treatment

Adrenal dysfunction is treated with steroids (such as cortisol).

A specific treatment for X-linked adrenoleukodystrophy is not available, but eating a diet low in very-long-chain fatty acids and taking special oils can lower the blood levels of very-long-chain fatty acids.

These oils are called Lorenzo's oil, after the son of the family who discovered the treatment. This treatment is being tested for X-linked adrenoleukodystrophy, but it does not cure the disease and may not help all patients.

Bone marrow transplant is also being tested as an experimental treatment.

Expectations (prognosis)

The childhood form of X-linked adrenoleukodystrophy is a progressive disease that leads to a long-term coma (vegetative state) about 2 years after neurological 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.

Complications

• Adrenal crisis
• Vegetative state (long-term coma)

Calling your health care provider

Call your health care provider if:

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

Prevention

Genetic counseling is recommended for prospective parents with a family history of X-linked adrenoleukodystrophy. Female carriers can be diagnosed 85% of the time using a very-long-chain fatty acid test and a DNA probe study done by specialized laboratories.

Prenatal diagnosis of X-linked adrenoleukodystrophy is also available. It is done by evaluating cells from chorionic villus samplingor amniocentesis.

References

Johnston MV. Neurodegenerative disorders of childhood. In: Kliegman RM, Behrman RE, Jenson HB, Stanton BF, eds. Nelson Textbook of Pediatrics. 18th ed. Philadelphia, Pa: Saunders Elsevier;2007:chap 599.

Answer 2

Definition

Adrenoleukodystrophy describes several closely related inherited disorders that disrupt the breakdown (metabolism) of certain fats (very-long-chain fatty acids).

Alternative Names

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

Causes, incidence, and risk factors

Adrenoleukodystrophy is passed down from parents to their children as an X-linked genetic trait. It therefore affects mostly males, although some women who are carriers can have milder forms of the disease. It affects approximately 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, which disrupts normal activity. There are three major categories of disease:

• Childhood cerebral form -- appears in mid-childhood (at ages 4 - 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

Symptoms

Childhood cerebral type:

• Changes in muscle tone, especially muscle spasms and spasticity
• Crossed eyes(strabismus)
• Decreased understanding of verbal communication (aphasia)
• Deterioration of handwriting
• Difficulty at school
• Difficulty understanding spoken material
• Hearing loss
• Hyperactivity
• Worsening nervous system deterioration
  • Coma
  • Decreased fine motor control
  • Paralysis
• Seizures
• Swallowing difficulties
• Visual impairment or blindness

Adrenomyelopathy:

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

Adrenal gland failure (Addison type):

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

Signs and tests

• Blood levels
• Chromosome study to look for changes (mutations) in the ABCD1 gene
• MRI of the head

Treatment

Adrenal dysfunction is treated with steroids (such as cortisol).

A specific treatment for X-linked adrenoleukodystrophy is not available, but eating a diet low in very-long-chain fatty acids and taking special oils can lower the blood levels of very-long-chain fatty acids.

These oils are called Lorenzo's oil, after the son of the family who discovered the treatment. This treatment is being tested for X-linked adrenoleukodystrophy, but it does not cure the disease and may not help all patients.

Bone marrow transplant is also being tested as an experimental treatment.

Expectations (prognosis)

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.

Complications

• Adrenal crisis
• Vegetative state (long-term coma)

Calling your health care provider

Call your health care provider if:

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

Prevention

Genetic counseling is recommended for prospective parents with a family history of X-linked adrenoleukodystrophy. Female carriers can be diagnosed 85% of the time using a very-long-chain fatty acid test and a DNA probe study done by specialized laboratories.

Prenatal diagnosis of X-linked adrenoleukodystrophy is also available. It is done by evaluating cells from chorionic villus samplingor amniocentesis.

References

Kwon JM. Neurodegenerative disorders of childhood. In: Kliegman RM, Behrman RE, Jenson HB, Stanton BF, eds. Nelson Textbook of Pediatrics. 19th ed. Philadelphia, Pa: Saunders Elsevier;2011:chap 592.

Reviewed By

Review Date: 12/01/2011

John Goldenring, MD, MPH, JD. Pediatrician with the Sharp Rees-Stealy Medical Group, San Diego, CA. Review provided by VeriMed Healthcare Network. Also reviewed by David Zieve, MD, MHA, Medical Director, A.D.A.M., Inc.