by Kimberly Allen, RN
X-linked adrenoleukodystrophy or X-ALD is a rare but serious and progressive disorder that affects approximately 1 in every 17,000 newborns every year. It affects people of all races and ethnic groups worldwide. X-ALD is the most common subtype of the adrenoleukodystrophies (ALD). ALD’s are considered peroxisomal disorders. Peroxisomal disorders are a group of inherently diverse metabolic disorders that have mutual dysfunction of peroxisomes. Peroxisomes play a crucial role in the metabolic pathway. These peroxisomes are responsible for breaking down long chain fatty acids. When there is a malfunction with the peroxisomes it causes a build up of saturated fatty acids in the adrenal cortex and the brain which in turn damages the myelin sheath that coats and protects the brain and the nerves as well as the adrenal gland.
Because X-ALD is an X linked disorder it involves the X chromosome. Because boys are born with only one X chromosome they will always be affected if the X-ALD gene is present. On the other hand, girls have 2 X chromosomes so if 1 has the X-ALD gene the other normal copy of X chromosome will dominate preventing X-ALD from developing. However, they will be carriers and can pass the X-ALD gene on to any children.
There are several types of X-ALD. Childhood cerebral ALD affects only boys and is the most severe form of the disorder. In a child born with this type of X-ALD symptoms usually manifest when the child is between 2 and 10 years of age. In the beginning, your child may demonstrate behavioral changes and a poor memory as well as developmental regressions. There is usually a slowing of thought processes as well as physical activity. As the disorder progresses the symptoms become more serious and can include the loss of vision and hearing, seizures and progressive dementia. Your child will also have difficulty speaking and swallowing as well as problems with coordination and walking. Because the adrenal glands are affected as the disorder progresses your child will also develop Addison disease. Another form of X-ALD is adolescent cerebral ALD which is similar to childhood cerebral ALD except that it usually manifests between 11 to 21 years of age and progresses more slowly. The most common type of X-ALD is adrenoleudoneuropathy or AMN. This type of X-ALD usually manifests in the 20’s and progresses slowly. The symptoms associated with this type include clumsiness and weakness as well as nausea and weight loss. People with this type tend to develop emotional problems like depression. They also tend to have problems with their motor function like walking. Some women that are carriers of the X-ALD gene develop symptoms similar to this type, however, they usually develop later and are usually milder than in men that are affected. There is even a type of X-ALD that affects only women known as symptomatic heterozygotes. The symptoms can vary fro mild to severe and usually don’t affect the adrenal glands.
There is currently no known cure for X-ALD, however, cortisone replacement can be given to treat the adrenal insufficiency. there are a variety of clinical trials taking place and experimental treatments available including bone marrow transplants. There is also promising research involving a drug call pioglitazone. In mice affected with X-ALD that were given oral doses of pioglitazone researchers were able to show that it “restored mitochondrial content and expression of master regulators of biogenesis”. It also neutralized the oxidative damage to proteins as well as DNA. The most important thing they discovered is that the treatment stopped the locomotor problems as well as axonal damage. Researchers are hopeful that these results will lead to clinical trials in patients with X-ALD.
In the past, the mortality rate with most types of X-ALD were extremely high with many children dying before they reached 5 years of age. However, with ongoing research there is hope for a future for many of the children affected with X-ALD.
Kimberly Allen is a registered nurse with an AND in nursing. She has worked in ACF, LCF and psychiatric facilities, although she spent most of her career as a home health expert. She is now a regular contributor to HealthAndFitnessTalk.com, dispensing advice and knowledge about medical issues and questions. You can reach her with any comments or questions at firstname.lastname@example.org.