Adrenoleukodystrophy, X-Linked (ABCD1)
X-linked adrenoleukodystrophy is a pan-ethnic disorder caused by pathogenic variants in the gene ABCD1. It is inherited in an X-linked manner, and therefore males are affected more often and more severely than females. Women who are carriers of adrenoleukodystrophy typically do not have any symptoms, although about 20% will develop mild symptoms later in life. This disorder affects the nervous system and is very variable in its clinical presentation. There are three main forms of the disease, known as the childhood cerebral form, adrenomyeloneuropathy, and Addisons disease. Boys who have the childhood cerebral form begin losing cognitive and behavioral skills between 4 to 8 years old and become fully disabled within several years. Death usually occurs in childhood or adolescence. Adrenomyeloneuropathy is characterized by onset in the patients 20s or 30s with weakness and stiffness in the legs, loss of sphincter control and sexual dysfunction. These symptoms increase in severity over time. Approximately half of these patients will develop neurological symptoms, and in some of these patients they will become so severe as to lead to total disability and death. Addisons disease is characterized by adrenal insufficiency, usually in childhood or adolescence. Most of these patients will develop adrenomyeloneuropathy by middle age. It is not currently possible to determine which phenotype a child will develop based on the inherited variants, or to predict the severity of the disease.
For information about carrier frequency and residual risk, please see the Expanded Carrier Screen brochure.