Adrenoleukodystrophy: Symptoms, Treatment Options, & Prognosis by Type

What is adrenoleukodystrophy?

Summary

Adrenoleukodystrophy is an inherited disorder that affects the adrenal glands and the nervous system. It is a rare disorder that affects males, leading to the abnormal buildup of fatty acids in the nervous system and adrenal glands, the glands that produce sex hormones and cortisol. The childhood form (childhood cerebral adrenoleukodystrophy) presents with cognitive and behavioral abnormalities and progresses to profound neurological damage and possibly death. The adult form (adrenomyeloneuropathy) presents primarily with weakness in the legs, sexual dysfunction, and bladder control problems, and progresses slowly over decades.

If untreated, the childhood form of this disorder can result in death or a vegetative state. Stem cell transplants and gene therapy are both promising in preventing neurologic decline in the childhood form of the disease. The adult form progresses more slowly over decades and may also benefit from gene therapy or other support.

Recommended care

You should visit your primary care physician, who will perform a blood test to rule in the diagnosis. Since this is a genetic condition, no cure is available, but steroids can be used if the adrenal gland is not making enough of its own.

Symptoms of adrenoleukodystrophy

The symptoms of each of the three types of ALD are described below. The types are childhood cerebral ALD (CCALD), adrenomyeloneuropathy (AMN), and adrenal form.

CCALD symptoms

Boys with this form will present between ages 4 and 8. Symptoms include:

• Learning disabilities
• Behavior problems: The child may be diagnosed with ADHD initially.
• Severe neurologic deterioration
• Blindness
• Paralysis
• Seizures
• Adrenal insufficiency symptoms: Such as fatigue, nausea, vomiting, and muscle weakness. They may also have hyperpigmented skin.

AMN symptoms

This form presents in adult males between ages 20 and 40. Symptoms include:

• Progressive stiffness and weakness of the legs
• Abnormal control of the bladder
• Sexual dysfunction
• Infertility
• Numbness and pain in hands and feet
• Adrenal insufficiency symptoms: Such as fatigue, nausea, vomiting, and muscle weakness. They may also have hyperpigmented skin.
• Similarities to the childhood form (CCALD): This includes cognitive or behavioral abnormalities, vision loss, or seizures.

Adrenal form symptoms

This form presents typically by age 10. Symptoms include those of adrenal insufficiency:

• Fatigue
• Nausea
• Vomiting
• Muscle weakness
• Possible hyperpigmented skin

What causes adrenoleukodystrophy?

Adrenoleukodystrophy is characterized as a rare genetic mutation and has no other known causes.

Genetic mutation details

The specific mutated gene, the ABCD1 gene, causes the resulting disease by:

• Protein encoding: The mutated ABCD1 gene encodes the adrenoleukodystrophy protein.
• Poor transport of fatty acids: This protein facilitates transport of very-long-chain fatty acids (VLCFA) into peroxisomes, the organelle in the cell that degrades and recycles fatty acids.
• Fatty acids build up: VLCFAs build up in the nervous system and adrenal glands, causing a spectrum of neurologic and adrenal dysfunction.

Who is most likely to be affected

This mutation is an X-linked disorder, which means females can carry the mutation and may have mild manifestations.However, males are most affected by the disease, approximately one in 15,000.

Treatment options and prevention for adrenoleukodystrophy

For asymptomatic people who have ALD, surveillance with MRI is common. Typically, other treatments are not initiated until symptoms start to occur.

Diagnosis and testing

The reason for you to be tested and the phase of life you are in will determine the testing type and any follow-up required.

• Newborn screening: In the United States, newborn screening is recommended but implementation varies by state. You can see if newborn testing occurs in your state here.The screening test looks for high levels of one specific, very-long-chain fatty acid, and is not a definitive test. Infants with a positive newborn screening test need to undergo confirmatory testing.
• Follow-up testing: Follow-up testing involves measuring the level of very-long-chain fatty acids in the blood. This level is elevated in nearly all people with the disorder. If this test is positive, genetic testing should be done to confirm the ABCD1 mutation is present.
• Imaging: Brain imaging is an adjunctive test following diagnosis of ALD. Typically, people with confirmed ALD will have repeat MRIs to image the brain and spinal cord. This is mainly to track progression over time.
• Electrophysiology: Electrophysiology is an adjunctive test following the diagnosis of ALD. These tests look at the function of specific parts of the nervous system. This can help track progress of visual loss, hearing loss, and loss of muscle or sensory nerve function.

Progression and prognosis

The progression and prognosis of this condition varies depending on the form experienced.

• CCALD: If left untreated, 90 percent of CCALD cases progress to total disability within six months to two years, and death within five to 10 years. If treated successfully, survival significantly improves. However, no treatment is curative and symptoms may continue to develop in adulthood.
• AMN: Unlike the childhood form of the disease, symptoms of AMN progress slowly over decades. Most people lose the ability to walk by age 50. There are currently no available treatments proven to slow or prevent progression of the disease.
• Adrenal form: People can be successfully treated with hormone replacement therapy. However, many will begin to develop neurologic symptoms by middle age, and have a similar course to people with AMN.

When to seek further consultation for adrenoleukodystrophy

If you have ALD in your family or you have been diagnosed with ALD, you should seek expert consultation. It is appropriated to be evaluated initially by a geneticist and a neurologist specializing in ALD.