Leukodystrophy refers to a group of more than 15 rare genetic disorders that cause progressive degeneration of the white matter of the brain due to imperfect growth or development of the myelin sheath, the fatty covering that acts as an insulator around nerve fiber. The leukodystrophies are often referred to as “demyelinating” diseases.
Myelin insulates nerve cells in the brain and spinal cord, helping them to transmit electrical nerve signals. Damage to this insulation slows down or blocks messages between the brain and the rest of the body. Without myelin, nerve cells cease to function and eventually die.
People with adrenoleukodystrophy, or ALD, do not produce an enzyme needed to break down fatty acids, resulting in high levels of saturated, very long chain fatty acids (VLCFA) in the brain and adrenal cortex. The progressive disabilities resulting from myelin loss and the progressive dysfunction of the adrenal gland are the primary characteristics of ALD. It occurs in one in every 40,000 male births and is the disease described in the book and 1992 Academy Award-nominated movie Lorenzo’s Oil.
ALD has two subtypes. The most common is the X-linked form (X-ALD), which involves an abnormal gene located on the X-chromosome. Women have two X-chromosomes and are the carriers of the disease, but since men only have one X-chromosome and lack the protective effect of the extra X-chromosome, they are more severely affected.
Onset of X-ALD can occur in childhood or in adulthood. The childhood form is most severe, with onset between ages 4 and 10. The most common symptoms are usually behavioral changes such as abnormal withdrawal or aggression, poor memory and poor school performance. Other symptoms include learning disabilities, vision loss, deafness, seizures, poorly articulated speech, difficulty swallowing, disturbances of gait and coordination, fatigue, intermittent vomiting, increased skin pigmentation and progressive dementia. In the milder adult-onset form, with onset typically between ages 21 and 35, symptoms may include progressive stiffness, weakness or paralysis of the lower limbs and ataxia.
Although adult-onset ALD progresses more slowly than the classic childhood form, it can also result in deterioration of brain function. A mild form of ALD is occasionally seen in women who are carriers of the disorder. Symptoms include progressive stiffness, weakness or paralysis of the lower limbs, ataxia, excessive muscle tone, mild peripheral neuropathy and urinary problems.
Prognosis for patients with ALD is generally poor due to progressive neurological deterioration. Death usually occurs within 1 to 10 years after the onset of symptoms.
The most common leukodystrophies include Canavan disease, Krabbe disease, metachromatic Leukodystrophy (MLD), Childhood Ataxia with Central Nervous System Hypomyelination (CACH), Alexander disease and Refsum disease.
Find clinical trials here: ALD clinical trials