About Cerebral Adrenoleukodystrophy

Adrenoleukodystrophy (ALD) is a rare genetic brain disorder that is estimated to affect approximately one in 20,000 people worldwide. Cerebral Adrenoleukodystrophy (CALD), the most severe form of ALD, is characterized by a breakdown of the protective sheath, called myelin, which surrounds and protects the nerve cells responsible for thinking and muscle control. As breakdown of the myelin occurs, the brain can no longer function properly, and symptoms rapidly progress within a matter of months or years. Symptoms usually occur in early childhood and progress rapidly, if untreated, and can cause a vegetative state, ultimately leading to death.

Symptoms of CALD usually occur in a boy’s early childhood and may include hyperactivity, visual disturbances, auditory problems, impaired coordination, memory loss and seizures.

CALD is an X-linked disorder, meaning it is a disease that affects mostly boys. Boys have one X‑chromosome, while girls have two. If a boy inherits the disease-causing, or malfunctioning, gene, unlike a girl, he does not have another copy of the gene to help compensate for the malfunctioning gene. CALD is caused by malfunctioning ABCD-1.

Boys with CALD do not produce enough or any of the adrenoleukodystrophy protein, or ALDP. The lack of ALDP causes cells in the brain to collect and store too many very long chain fatty acids. These fatty acids are harmful to brain cells and are responsible for the breakdown of myelin and inflammation.

Diagnosing CALD can be difficult because initial symptoms are similar to other disorders, including attention deficit hyperactivity disorder (ADHD), autism, epilepsy and learning disabilities. In addition, many physicians are not aware of CALD or may not look for it, because it is so rare. Most physicians, even pediatric specialists, may not see a single case of CALD during their careers.

It is important that CALD is diagnosed as early as possible. Research shows that available treatments are most effective either before symptoms develop or soon after they start. Once the disease progresses and becomes severe, the lost myelin cannot be replaced and damage to the brain cannot be reversed. 

Currently, the only effective treatment option is allogeneic hematopoietic stem cell transplant (HSCT). This is a medical procedure in which a patient receives stem cells from a donor who does not have CALD.

The best results for allogeneic HSCT occur with stem cells from a donor with a matching tissue type, usually a sibling. However, less than 30 percent of patients who are candidates for transplantation have a sibling with such a match.

If an allogeneic HSCT is performed using a matched or mismatched unrelated donor, a possible outcome is graft-verus-host disease (GVHD), which occurs when the donated cells attack the patient’s cells, because they appear foreign. Graft rejection, when the patient’s body attacks the donated cells, also is possible. GVHD and graft rejection are serious complications and GVHD is a prominent cause of death. While allogeneic HSCT is an effective treatment for CALD, results are not always optimal, and additional treatment options are needed.