Adrenoleukodystrophy (X-Linked)

Definition

Definition of Adrenoleukodystrophy (X-Linked)
X-linked adrenoleukodystrophy is a disorder that occurs most often in males. It mainly affects the nervous system and the adrenal glands, which are 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 a shortage of certain hormones caused by damage to the outer layer of the adrenal glands (adrenal cortex). This hormonal deficiency is known as adrenocortical insufficiency.

Symptoms

Symptoms of Adrenoleukodystrophy (X-Linked)
Signs and symptoms of the adrenomyeloneuropathy type appear between early adulthood and middle age. Affected individuals develop progressive stiffness and weakness in their legs (paraparesis), experience urinary and genital tract disorders, and often show some degree of brain dysfunction. Most people with the adrenomyeloneuropathy type also have adrenocortical insufficiency.

When adrenocortical insufficiency occurs without any other symptoms it is sometimes called Addison disease. People with X-linked adrenoleukodystrophy whose only symptom is adrenocortical insufficiency are said to have the Addison disease only form. Adrenocortical insufficiency may cause weakness, weight loss, skin changes, vomiting, and coma. Most people initially diagnosed with the Addison disease only form of X-linked adrenoleukodystrophy eventually develop all the signs of adrenomyeloneuropathy by the time they reach middle age.

Causes

Causes of Adrenoleukodystrophy (X-Linked)
This condition is inherited in an X-linked 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 each cell. In males (who have only one X chromosome), one altered copy of the gene in each cell is sufficient to cause the condition. Because females have two copies of the X chromosome, one altered copy of the gene in each cell usually leads to less severe symptoms in females than in males, or may cause no symptoms at all.

Many females who carry one altered copy of the ABCD1 gene do not have any features of X-linked adrenoleukodystrophy; however some females with one altered copy of the gene have medical problems associated with this disorder. The signs and symptoms of X-linked adrenoleukodystrophy tend to appear at a later age in females than in males. In affected women, the disorder is usually similar to the adrenomyeloneuropathy type, although it may occasionally impair adrenal gland function. Less commonly, affected females have signs of the childhood cerebral form of this condition.

Diagnosis

Diagnosis of Adrenoleukodystrophy (X-Linked)
The diagnosis of X-ALD is based on clinical findings. MRI is always abnormal in males with neurologic symptoms and often provides the first diagnostic lead. Plasma concentration of very long chain fatty acids (VLCFA) is abnormal in 99% of males with X-ALD. Increased concentration of VLCFA in plasma and/or cultured skin fibroblasts is present in approximately 85% of affected females; 20% of known carriers have normal plasma concentration of VLCFA. Molecular genetic testing of ABCD1, the only gene known to be associated with X-ALD, is clinically available.

Treatment

Treatment of Adrenoleukodystrophy (X-Linked)
Corticosteroid replacement therapy is essential for those with adrenal insufficiency. Affected boys benefit from the general supportive care of parents and psychological and educational support. Physical therapy, management of urologic complications, and family and vocational counseling are of value for men with AMN.

Prognosis

Prognosis of Adrenoleukodystrophy (X-Linked)
Consult with your doctor.

Prevention

Prevention of Adrenoleukodystrophy (X-Linked)
There is no way to prevent ALD. 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. This is especially true in young boys who are treated with Lorenzo’s oil. New technologies may soon allow early identification through newborn screening.