Adrenoleukodystrophy Health Article

Definition

Adrenoleukodystrophy (ALD) is a progressive condition that affects both the adrenal glands (located atop the kidneys and responsible for the production of adrenalin) and myelin (the substance that insulates the nerves in the brain, spinal cord, and the limbs).

Description

First described in the early 1900s, adrenoleukodys-trophy was originally called Schilder-Addision disease. "Adreno" refers to the adrenal glands, "leuko" is the Greek word for white (myelin is the main component of the white matter in the brain and spinal cord), and "dystrophy" means impaired growth. This disease affects the adrenal glands and the growth of the myelin.

Types of ALD

There are three types of ALD, each with a different severity of symptoms and age of onset of ALD. All varying degrees of severity have been seen within the same family. Therefore, a family who has many mildly affected members could still have a more severely affected member. Some patients do not fall neatly into one of the three categories, and instead fall somewhere in between. Each type is given a different name, although all have mutations (changes in the genetic code) in the same gene and the same type of inheritance.

The most severe form of ALD is called childhood ALD. About 35% of people with ALD have this type. These children usually have normal development in the first few years of life. Symptoms typically begin between four and eight years of age. Very rarely is the onset before the age of three or after the age of 15. In some boys, the first symptom may be seizures. Other children become hyperactive and have behavioral problems that may initially be diagnosed as attention deficit/hyperactivity disorder (ADHD). Early signs may also include poor school performance due to impaired vision that is not correctable by eyeglasses. Although these symptoms may last for a few months, other more severe problems develop. These include increasing problems with schoolwork and deterioration in handwriting and speech. Affected children usually develop clumsiness, difficulty in reading and comprehension of written material, aggressive or uninhibited behavior, and various personality and behavioral changes. Most affected boys have problems with their adrenal glands by the time their first symptoms are noticed.

A milder form of ALD, called adrenomyeloneuropathy (AMN), usually has a symptom onset at the age of 20 or later. Approximately 40–45% of people with ALD have AMN. The first symptoms are typically a progressive stiffness and weakness in the legs. Problems with urination and sexual function may also develop. Symptoms slowly progress over many years. Less than 20% of men with AMN will develop significant brain involvement that leads to cognitive and behavioral problems that are severe and may cause a shortened lifespan. About 70% of men with AMN will have problems with their adrenal glands when other symptoms are initially noticed.

A third type of ALD is called Addison disease and affects about 10% of all of those with ALD. In this condition, people do not have the neurologic symptoms associated with ALD and AMN, but they do have problems resulting from adrenal insufficiency. Symptoms typically begin between two years of age and adulthood. The first symptoms are often vomiting, weakness, or coma. People with Addision disease may or may not have darker skin. Many who are initially diagnosed with Addison disease will later develop symptoms of AMN.

In female carriers of ADL, about 20% will develop mild to moderate progressive stiffness and weakness in the legs and sometimes problems with urination. Rarely do they develop adrenal insufficiency. Symptoms in women generally do not begin before middle age.

Demographics

ALD is found in all ethnic groups. About one in every 100,000 people suffers from ALD. Because the most severe form, called classic ALD, is X-linked, many more males than females are affected. Women are carriers of this X-linked form of the disease and may exhibit no or only mild symptoms. Another form of the disease is called neonatal ALD; this form of ALD is not X-linked and therefore both male and female babies exhibit symptoms. An adult-onset type of the disease is commonly called adrenomyeloneuropathy.