Adrenoleukodystrophy, also known as ALD, is a hereditary disorder that affects the myelin sheath that covers nerve cells in the brain. This disorder affects mostly males, and rarely affects females. Substances known as c-24 and c-26 are found in patients’ blood in a concentration that is four times higher than in healthy people, these substances harm the myelin fatty covering insulating the nerves.
What are the causes for adrenoleukodystrophy?
The most common type of ALD is caused by a mutation in a gene located on the X chromosome. For this reason, this disorder affects mostly men (women have two X chromosomes, so if a mutated gene is inherited, the second chromosome can compensate for the mutation). This mutation causes a buildup of very long chain fatty acids (VLCFA) made of 24-30 carbon atoms.
The gene mutation causing this disease was discovered in 1993 and as of today, the mechanism linking the fatty acid buildup to myelin loss remains unclear. Unlike many genetic diseases, the mutated gene is not coded to produce enzymes, but to the production of a protein that transports fatty acids to the peroxisome.
When this transporter does not function normally, very long chain fatty acids cannot undergo beta-oxidation and their levels in the blood begin to rise fatally. Mutations in other genes may also cause this disorder, but these are inherited in an autosomal inheritance pattern and are not x linked. These genes include PEX28, PEZ10, PEX13, PEX5 and PEX1.
What are the symptoms?
The disease usually develops between ages 4-12 years. The prevalence of ALD is 1 in 10,000 people. Initial symptoms diagnosed usually include learning difficulties, behavioral changes, impaired vision and hearing, lack of balance, and seizures.
These symptoms progressively worsen and eventually lead to a vegetative state and death within 1-10 years from the onset of the disease.
How is adrenoleukodystrophy diagnosed?
Since ALD is a rare disorder, screening tests for it are not commonly offered. Testing is usually only done after initial symptoms appear. The first test usually performed is a simple blood draw that checks for high levels of VLCFA (very long chain fatty acids).
If high levels of VLCFA are detected, further genetic tests are required for testing relevant genes. In addition, people with ALD often show typical changes in affected organs, detectable via skin biopsies or imaging tests such as MRI or CT.
Can ALD be diagnosed prenatally?
ALD is a rare disorder and as such, testing for this condition is usually not offered to the general population as part of prenatal screening tests or preconception testing. However, women who have a family history of at least one family member with ALD can request to undergo genetic testing to find out whether they are carriers of the gene mutation.
Women who are diagnosed as carriers can also detect the mutated gene via amniocentesis or chorionic villus sampling.
