X-Linked Adrenoleukodystrophy

What is X-linked adrenoleukodystrophy?

X-linked adrenoleukodystrophy is a disorder that mainly affects the nervous system and the adrenal glands (small glands located on top of each kidney). People with this disorder often have progressive destruction of the fatty covering (myelin) that insulates nerves in the brain and spinal cord. They may also have hormone deficiencies caused by damage to the outer layer of the adrenal glands (adrenal cortex). This hormonal deficiency is also known as adrenocortical insufficiency.

In males, there are three distinct types of X-linked adrenoleukodystrophy: a childhood cerebral form, adrenomyeloneuropathy, and a type called Addison disease only. Male children with the cerebral form of this disorder experience learning and behavioural problems that usually appear by age 10. Over time the symptoms worsen and these children may have difficulty reading, writing, understanding speech, and comprehending written material. They may also exhibit aggressive behaviour and have vision problems. Most affected individuals also have impaired adrenal gland function. The rate at which this disorder progresses is variable; however, total disability within several years is not uncommon.

Signs and symptoms of the adrenomyeloneuropathy type appear in men anytime between their twenties and middle age. These men develop progressive stiffness and weakness in their legs (paraparesis), urinary disorders, and often show some degree of brain involvement. Most men with this disorder also have adrenocortical insufficiency.

The Addison disease only form affects approximately 10 percent of males with X-linked adrenoleukodystrophy. This form is characterised primarily by adrenocortical insufficiency, which may result in unexplained weakness, weight loss, skin changes, vomiting, and coma. Most men with this condition eventually develop all of the signs of adrenomyeloneuropathy by the time they reach middle age.

Females are affected by X-linked adrenoleukodystrophy far less often than males. When females do have signs of this disorder, they are usually similar to the adrenomyeloneuropathy type, although they rarely exhibit impaired adrenal gland function. In rare cases, females have signs of the childhood cerebral form of this condition.

How common is X-linked adrenoleukodystrophy?

The prevalence of X-linked adrenoleukodystrophy is approximately 1 in 20,000 individuals. This condition occurs with a similar frequency in all populations.

What genes are related to X-linked adrenoleukodystrophy?

Mutations in the ABCD1 gene cause X-linked adrenoleukodystrophy.

Mutations in the ABCD1 gene cause a shortage (deficiency) of a cellular transporter known as adrenoleukodystrophy protein. This protein is thought to play a role in the breakdown of certain fats (very long-chain fatty acids or VLCFAs) inside peroxisomes. Peroxisomes are small sacs in the cell that process many types of molecules. When this transporter is lacking, the breakdown of very long-chain fatty acids is compromised and results in abnormally high levels of these fats in the body. Research suggests that the accumulation of very long-chain fatty acids is toxic to the adrenal cortex and the myelin membranes that surround many of the nerves in the brain and spinal cord.

How do people inherit X-linked adrenoleukodystrophy?

This condition is inherited in an X-linked recessive pattern. A condition is considered X-linked if the mutated gene that causes the disorder is located on the X chromosome, one of the two sex chromosomes. In males (who have only one X chromosome) one altered copy of the gene in each cell is sufficient to cause the condition. Males are affected by X-linked recessive disorders much more frequently than females. A striking characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons.

All of the daughters of a male with an X-linked disorder will inherit the gene mutation. These females are called carriers because they carry one copy of the altered gene. In females (who have two X chromosomes), a mutation must usually be present in both copies of the gene to cause the disorder. In some cases, however, females who are carriers of a gene mutation on the X chromosome will exhibit signs and symptoms of a disorder beginning in adulthood.

What other names do people use for X-linked adrenoleukodystrophy?

* Adrenoleukodystrophy
* Adrenomyeloneuropathy
* Schilder-Addison Complex

Medic8® Genetic Disorders

Page last modified: September 2006

Source: NIH