Adrenoleukodystrophy (ALD) is a rare inherited genetic disorder. ALD results in degeneration of:

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

• The adrenal gland

There are several types of ALD. The two most common types are: X-linked (also called child-onset ALD) and neonatal.

Causes

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 (which covers the 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 ALD include:

• Having a mother who carries the defective ALD gene

• Age: Childhood

• Sex: Male

Symptoms

Symptoms can vary within the types of ALD.

X-linked ALD (Child-onset)

X-linked ALD is the most severe form of the disease. This type only affects boys. Symptoms usually begin between the ages of 4-10 years. About 35% of patients can experience severe symptoms during the early phase.

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

Neonatal ALD

Neonatal ALD can affect both male and female newborns since the abnormal genes that cause the disease in neonates are not located on the X chromosome. Symptoms of neonatal ALD can be severe and progress quickly. They can include:

• Facial abnormalities

• Mental retardation

• Seizures, often starting on the first day of life

• Degeneration of the retina

• Muscle tone problems

• Liver problems

• Adrenal gland dysfunction

Adult-onset ALD

With adult-onset ALD, (possibly a milder form of neonatal ALD) symptoms usually do not appear until young adulthood. It usually progresses much slower than child-onset ALD. Ultimately, however, adult-onset ALD can cause deterioration of brain function and the same serious symptoms seen in child-onset ALD.

Ovarioleukodystrophy

This form of ALD is generally seen only in women. It can cause the loss of ovarian function. Symptoms include:

• Weakness or paralysis of the lower limbs, resulting in difficulty walking (ataxia)

• Muscle tone problems

• Visual problems

• Urinary problems

• Progressive dementia

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 may be done.

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

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.