The History of Adrenoleukodystrophy

Adrenoleukodystrophy, also known by the acronym ALD, is a genetic disorder characterized by the damage of the myelin sheath, a tissue that protects the nerve cells of the brain. This causes to progressive brain damage, as well as the dysfunction of the adrenal glands, which produce hormones that control metabolism, fluid balance and blood pressure. ALD is classified as a leukodystrophy--a medical condition that involves progressive degeneration of the white matter of the brain.

Discovery

• The first case of ALD was described by a pair of physicians, Haberfeld and Spieler, in 1910 when they observed a pair of brothers. The younger of the two boys was in good health at 6 years of age until he developed a deeply bronzed skin tone, failing vision and plummeting school performance. By the next year, he began to have difficulty walking and eventually was hospitalized. At the last stages of his affliction, he lost the ability to speak and finally passed away eight months after his hospitalization.

Siemerling-Creutzfeldt Disease/Schilder's disease

• Noting that the elder of the two brothers that Haberfeld and Spieler had examined died under similar circumstances at the age of 8, another doctor, Paul Ferdinand Schilder, examined the brains of both brothers in 1913 to discover severe loss of myelin. A decade later, Ernst Siemerling and Hans Creutzfeldt came across a boy with a similar condition. This time, they documented the disorder's adverse effect on the adrenal glands. For this reason, ALD was previously named after these three physicians: "Siemerling-Creutzfeldt Disease" or "Schilder's disease."

Official Classification

• In 1952, physicians Adams and Kubic suggested that the condition should be placed in the same category as multiple sclerosis, since both diseases share the same trait of myelin loss, although they noted that ALD had a more severe case of degeneration. By 1963, researchers had noted that all the patients up to this point have been males, thus suggesting a X-linked recessive inheritance. Due to its link of brain degeneration with adrenal insufficiency, the term "adrenoleukodystrophy" was introduced in 1970.

X-ALD

• By 1977, enough research had been done for the medical community to label the most common form of ALD as "X-ALD," which usually occurs between childhood and adulthood. X-ALD involves an abnormal gene on the X-chromosome, which particularly affects men because they lack the extra X-chromosome that women have as a protective agent. The other, milder and rarer form of the disease--adult-onset ALD--usually occurs in men between the ages 21 and 35, and may also occur in women who are carriers of the disorder. In 1981, the ALD gene was mapped to the chromosome Xq28.

Today

• As of 2010, ALD research is primarily focused on preventing, treating and curing the disorder. In 1988, the first successful bone-marrow transplantation was performed on an ALD patient. In 2007 and 2008, a team of physicians led by Nathalie Cartier and Patrick Aubourg successfully treated a pair of 7-year-old boys with early signs of ALD using gene therapy. Other treatments so far discovered for ALD include physical therapy and administration of fatty acid mixtures.