X-linked Adrenoleukodystrophy
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X-linked Adrenoleukodystrophy

(Sudanophilic Leukodystrophy; Schilder’s Disease)

En Español (Spanish Version)

Definition

X-linked adrenoleukodystrophy (ALD) is a rare inherited genetic disorder. There have been 34 types of ALD described. X-linked ALD is the most common category. ALD results in degeneration of:

  • The fatty insulation covering on nerve fibers in the brain (myelin sheath)
  • The adrenal gland

Myelin Sheath Around Nerve Fiber

AX00010_97870_1_myelin_sheath

© 2008 Nucleus Medical Art, Inc.

There are six types of X-linked ALD:

  • Childhood cerebral ALD
  • Adolescent ALD
  • Adrenomyeloneuropathy
  • Adult cerebral ALD
  • Adrenal insufficiency-only
  • Symptomatic heterozygotes

Causes

X-linked ALD is caused by an inherited defective gene on the X chromosome, and is therefore called a “sex-linked” inherited disorder. In people with ALD, the body's enzymes do not properly break down fatty acids. This results in an accumulation of high levels of saturated fatty acids in the brain and the adrenal cortex, which causes degeneration of the myelin sheath (insulation covering on nerves) and the adrenal gland.

Risk Factors

A risk factor is something that increases your chances of getting a disease or condition. Risk factors for X-linked ALD include:

  • Having a mother who carries the defective X-linked ALD gene
  • Age: Childhood to young adult
  • Sex: Male, although females may be affected

Symptoms

Symptoms can vary within the types of ALD.

X-linked ALD (Childhood Cerebral ALD)

This form of X-linked ALD is the most severe form of the disease. This type only affects boys. Symptoms usually begin between the ages of 2 to 10 years of age. About 35% of patients can experience severe symptoms during the early phase. On average, death results in 2 years, although some patients may live a couple of decades.

Initial symptoms include:

  • Behavioral changes
  • Poor memory
As the disease progresses, more serious symptoms develop. These include:
  • Vision loss
  • Seizures
  • Hearing loss
  • Difficulty swallowing and speaking
  • Difficulty with walking and coordination
  • Vomiting
  • Fatigue
  • Increased pigmentation (“bronzing”) of the skin, due to adrenal hormone deficiency ( Addison’s disease )
  • Progressive dementia
  • Vegetative state or death

X-linked ALD (Adolescent Cerebral ALD)

This type is similar to the childhood type except the age group for presentation is 11 to 21 years old and the progression is usually slower.

Adrenomyeloneuropathy (AMN)

This is the most common form of X-linked ALD. Symptoms of AMN can present in the 20s, and progress slowly. They can include:

  • Weakness, clumsiness, weight loss, nausea
  • Emotional disturbances or depression
  • Muscle problems (e.g. walking problems)
  • Urinary problems or impotence
  • Adrenal gland dysfunction

X-linked ALD (Adult Cerebral ALD)

With adult cerebral ALD, symptoms usually do not appear until young adulthood (20s) or middle age (50s). It causes symptoms like someone with schizophrenia and dementia. It usually progresses fast, and results in death or a vegetative state in 3-4 years.

Symptomatic Heterozygotes

This form of ALD is seen only in women. Symptoms may be mild or severe, but usually does not affect the adrenal gland function.

Diagnosis

The doctor will ask about symptoms and medical history, and perform a physical exam. The doctor may suspect ALD from its symptoms. To confirm the diagnosis, blood tests, to look for increased amount of very long chain fatty acids may be done. An MRI of the brain may be done to look for brain involvement.

Treatment

There is no known cure for the neurologic defects of ALD. However, the adrenal deficiency can be successfully treated with cortisone replacement. ALD (especially the more severe forms) often causes death within 10 years of the onset of symptoms.

Some therapies can help to manage the symptoms of ALD. There are also some experimental treatments.

Therapies to help manage the symptoms of ALD include:

  • Physical therapy
  • Psychological therapy
  • Special education (for children)

Some treatments you may want to talk to your doctor about include:

  • Bone marrow transplant—this procedure may be most helpful when given early to boys with X-linked child-onset ALD
  • Dietary therapy, which includes consumption of:
    • A very low fat diet
    • “Lorenzo’s oil”—dietary supplements of glycerol trioleate and glycerol trierucate (oleic and euric acid)
  • Lovastatin—an anti-cholesterol medication

Prevention

There is no way to prevent ALD except by preventing the birth of affected children. If you have ALD or have a family history of the disorder, you can talk to a genetic counselor when deciding to have children. Early recognition and treatment may prevent the development of clinical symptoms, especially in young affected boys who are treated with Lorenzo’s oil. New technologies may soon allow early identification through newborn screening.

RESOURCES:

National Institute of Neurological Disorders and Stroke
http://www.ninds.nih.gov

National Organization for Rare Disorders
http://www.rarediseases.org

United Leukodystrophy Foundation
http://www.ulf.org

CANADIAN RESOURCES:

Canadian Directory of Genetic Support Groups
http://www.lhsc.on.ca/programs/medgenet/adrenole.htm

The Myelin Project of Canada
http://www.myelinprojectcanada.ca/About_Us.html

References:

The Merck Manual of Medical Information . Simon and Schuster, Inc.; 2000.

Moser HW. Therapy of X-linked adrenoleukodystrophy (review). NeuroRx. 2006 . Apr;3(2):246-53.

Moser HW, Raymond GV, Dubey P. Adrenoleukodystrophy: new approaches to a neurodegenerative disease. JAMA . 2005 Dec 28;294(24):3131-4.

Moser HW, Raymond GV, Lu SE, Muenz LR, Moser AB, Xu J, et al. Follow-up of 89 asymptomatic patients with adrenoleukodystrophy treated with Lorenzo's oil. Arch Neurol . 2005 Jul;62(7):1073-80.

The National Center for Biotechnology Information website. Available at: http://www.ncbi.nlm.nih.gov/.

National Institute of Neurological Disorders and Stroke website. Available at: http://www.ninds.nih.gov.



Last reviewed November 2007 by Mark A. Best, MD, MPH, MBA

Please be aware that this information is provided to supplement the care provided by your physician. It is neither intended nor implied to be a substitute for professional medical advice. CALL YOUR HEALTHCARE PROVIDER IMMEDIATELY IF YOU THINK YOU MAY HAVE A MEDICAL EMERGENCY. Always seek the advice of your physician or other qualified health provider prior to starting any new treatment or with any questions you may have regarding a medical condition.


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