What is ALD?

Adrenoleukodystrophy

Adrenoleukodystrophy, or ALD, is a deadly genetic disease that affects 1 in 17,000 people. As it is an X-linked genetic disease, which means, it most severely affects boys and men. ALD involves multiple organs in the body, but most prominently affects the brain and spinal cord. This brain disorder destroys myelin, the protective sheath that surrounds the brain’s neurons. Without the myelin sheath the nerve cells that allow us to think and to control our muscles no longer function correctly. ALD knows no racial, ethnic or geographic barriers.

ALD Overview

Childhood Cerebral ALD

Childhood Cerebral ALD is the most devastating form of ALD, it generally occurs between the ages of four and ten years old. Normal, healthy boys suddenly begin to regress. At first, they may simply show minor behavioral problems, such as withdrawal or difficulty concentrating, vision problems, or start to have coordination issues. Gradually, as the disease spreads throughout the brain, their symptoms grow worse, including blindness, deafness, seizures, loss of muscle control, and progressive dementia. This relentless downward spiral leads to a vegetative state or die usually within 2-5 years of diagnosis.

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What is myelin (white matter) and why is it so important in the nervous system?

Myelin constitutes the “white matter” of the brain. It consists of fatty acid molecules, and provides the protective covering of the nerve cells, similar to insulation surrounding an electric wire. Myelin is required for the rapid, precise transmission of information to and from neurons throughout the brain and spinal cord. Demyelination is the stripping away of the fatty coating (white matter) that keeps nerve pulses confined and maintains the integrity of nerve signals. This process inhibits the nerves ability to conduct properly, thereby causing neurological deficits. In childhood cerebral ALD, not only do cells undergo demyelination, but there is also an inflammatory response, all of which destroy the brain.

When myelin is damaged, communication is lost during transmission. This results in the loss of voluntary and involuntary functions in the body.

Currently there is no known treatment to reverse damaged myelin, although there are options to manage symptoms. Proactive, comprehensive medical care will allow families and caregivers to give the affected individual the best quality of life possible. Furthermore, through ALD Newborn Screening, affected children have the opportunity to benefit from lifesaving treatment, which can halt the disease (see Treatment Section).

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What causes ALD? And why does the disease typically impact boys?

ALD is caused by mutations in ABCD1, a gene located on the X chromosome that codes for ALD, Protein (ALDP), which functions as a peroxisomal membrane transporter. The transporter is required for the normal turn over, or metabolism, of fatty acids in the brain and spinal cord. Without the transporter, the normal metabolism of fatty acids does not occur. Therefore, the brain and spinal cord undergo demyelination. Biochemically, individuals with ALD show very high levels of unbranched, saturated, very long chain fatty acids, particularlycerotic acid (26:0).

The damaged gene that causes ALD resides on the X Chromosome. Boys inherit only one X Chromosome, which is passed to them from their mothers. Because girls inherit two X Chromosomes, one from each parent, the functional copy inherited from their father usually protects female children from the disease. However, females with the mutation are carriers who can pass the disease on to their male offspring. It is possible – but rare for girls to inherit 2 copies of the mutation from both parents.

How do you get ALD?

ALD disease is a genetic, or inherited, disorder. If a mother is a carrier of ALD, there is a 50% chance of passing this on to her children.

If a father is a carrier of ALD, he will pass this on to his daughter 

Spontaneous mutations are another way a baby can inherit ALD. This means that the mother and father are not carriers of ALD, but the mutation of the gene causing ALD happens in utero. Spontaneous mutations arise from a variety of sources, including errors in DNA replication, spontaneous lesions, and transposable genetic elements.

How does ALD affect the individual?

ALD is a multisystem disease, but most prominently affects both the central and peripheral nervous systems, which are responsible for all of the body’s voluntary and involuntary functions.

Damage to the brain results in blindness, seizures and hyperactivity. Other effects include problems with speaking, listening, and understanding verbal instructions.

Damage to the spinal cord results in the loss of the ability to walk and maintain normal breathing.

The most severely affected tissues outside of the nervous system are the adrenal cortex, and the Leydig cells in the testes. Damage to the adrenal cortex results in adrenal insufficiency or Addison’s Disease. Damage to the testes results in infertility.

The rate of progression depends on what form of the disease the individual has.

With proactive, comprehensive medical care the symptoms of ALD can be managed and give the individual the best quality of life possible. Furthermore, through ALD newborn screening, affected children have the opportunity to benefit from lifesaving treatment.

Who else in my family needs to be tested for ALD?

If a mother has ALD, there is a 50% chance of each of her other children also having ALD. This is crucial if the child is male and they should be tested immediately. If there are other female children, they can be tested when they are of childbearing age. Extended family – sisters, brothers, aunts, uncles, nieces, and nephews of the affected parent should also be tested for ALD.

To determine if other children in the family are affected by or carriers of ALD disease, it is best to consult with your genetic counselor or your child’s primary care physician.

You can also request a blood spot card from the Kennedy Krieger Institute.

The requisition form may be downloaded HERE 

Results are available within 7 to 10 days, unless there are special circumstances.

Contact information related to testing:

Kennedy Krieger Institute Genetics Laboratory - Peroxisomal Diseases Section 
707 North Broadway
Baltimore, MD 21205 USA

Phone: +1.443.923.2760
Fax: +1.443.923.2755

How is ALD diagnosed?

ALD is diagnosed through a blood test, which analyzes the amount of very long chain fatty acids, which are elevated in ALD.

An MRI diagnoses cerebral ALD.

Although newborn screening for ALD is available in some states it is NOT a diagnostic test. Newborn screening can, however, lead to a proper and early diagnosis upon confirmatory testing.

ALD Newborn Screening is currently active in 9 states: New York, Connecticut, California, Minnesota, Pennsylvania, Washington, Tennessee, Florida and Nebraska. More states are slated to come on board in late 2018/2019. If you currently live in a state which is not testing or have extended family living in a state that is not testing, please contact the Kennedy Krieger Laboratory, listed above, for a blood spot card.