Adrenoleukodystrophy

What is Adrenoleukodystrophy?

Adrenoleukodystrophy (ALD) is one of a group of genetic disorders called the leukodystrophies that cause damage to the myelin sheath, an insulating membrane that surrounds nerve cells in the brain. People with ALD accumulate high levels of saturated, very long chain fatty acids (VLCFA) in the brain and adrenal cortex because they do not produce the enzyme that breaks down these fatty acids in the normal manner. The loss of myelin and the progressive dysfunction of the adrenal gland are the primary characteristics of ALD. ALD has two subtypes. The most common is the X-linked form (X-ALD), which involves an abnormal gene located on the X-chromosome. Women have two X-chromosomes and are the carriers of the disease, but since men only have one X-chromosome and lack the protective effect of the extra X-chromosome, they are more severely affected. Onset of X-ALD can occur in childhood or in adulthood. The childhood form is the most severe, with onset between ages 4 and 10. The most common symptoms are usually behavioral changes such as abnormal withdrawal or aggression, poor memory, and poor school performance. Other symptoms include visual loss, learning disabilities, seizures, poorly articulated speech, difficulty swallowing, deafness, disturbances of gait and coordination, fatigue, intermittent vomiting, increased skin pigmentation, and progressive dementia. In the milder adult-onset form, which typically begins between ages 21 and 35, symptoms may include progressive stiffness, weakness or paralysis of the lower limbs, and ataxia. Although adult-onset ALD progresses more slowly than the classic childhood form, it can also result in deterioration of brain function. A mild form of ALD is occasionally seen in women who are carriers of the disorder. Symptoms include progressive stiffness, weakness or paralysis of the lower limbs, ataxia, excessive muscle tone, mild peripheral neuropathy, and urinary problems.

Is there any treatment?

Adrenal function must be tested periodically in all patients with ALD. Treatment with adrenal hormones can be lifesaving. Symptomatic and supportive treatments for ALD include physical therapy, psychological support, and special education. Recent evidence suggests that a mixture of oleic acid and erucic acid, known as "Lorenzo's Oil," administered to boys with X-ALD can reduce or delay the appearance of symptoms. Bone marrow transplants can provide long-term benefit to boys who have early evidence of X-ALD, but the procedure carries risk of mortality and morbidity and is not recommended for those whose symptoms are already severe or who have the adult-onset or neonatal forms. Oral administration of docosahexanoic acid (DHA) may help infants and children with neonatal ALD.

What is the prognosis?

Prognosis for patients with ALD is generally poor due to progressive neurological deterioration. Death usually occurs within 1 to 10 years after the onset of symptoms.

What research is being done?

The NINDS supports research on genetic disorders such as ALD. The aim of this research is to find ways to prevent, treat, and cure these disorders. Intensive basic research has proposed two new approaches, 4-phenylbutyrate and lovastatin, which could potentially lower levels of VLCFA in the brain. Therapeutic trials for both agents are planned.

NIH Patient Recruitment for Adrenoleukodystrophy Clinical Trials

• At NIH Clinical Center
• Throughout the U.S. and Worldwide
• NINDS Clinical Research Collaboration Trials

Organizations

National Organization for Rare Disorders (NORD) P.O. Box 1968 (55 Kenosia Avenue) Danbury, CT   06813-1968 orphan@rarediseases.org http://www.rarediseases.org Tel: 203-744-0100 Voice Mail 800-999-NORD (6673) Fax: 203-798-2291	National Tay-Sachs and Allied Diseases Association 2001 Beacon Street Suite 204 Boston, MA   02135 info@ntsad.org http://www.ntsad.org Tel: 800-90-NTSAD (906-8723) Fax: 617-277-0134
United Leukodystrophy Foundation 2304 Highland Drive Sycamore, IL   60178 office@ulf.org http://www.ulf.org Tel: 815-895-3211 800-728-5483 Fax: 815-895-2432	Myelin Project P.O. Box 39 Pacific Palisades, CA   90272 margaret.weis@myelin.org http://www.myelin.org Tel: 800-869-3546 310-459-1071 Fax: 310-230-4298

Prepared by:
Office of Communications and Public Liaison
National Institute of Neurological Disorders and Stroke
National Institutes of Health
Bethesda, MD 20892

NINDS health-related material is provided for information purposes only and does not necessarily represent endorsement by or an official position of the National Institute of Neurological Disorders and Stroke or any other Federal agency. Advice on the treatment or care of an individual patient should be obtained through consultation with a physician who has examined that patient or is familiar with that patient's medical history.

All NINDS-prepared information is in the public domain and may be freely copied. Credit to the NINDS or the NIH is appreciated.

Last updated March 18, 2009