Cerebral adrenoleukodystrophy (CALD) is a rare disorder that primarily affects young males. Without treatment, it can lead to a loss of motor and cognitive abilities and a shortened life span. But with early treatment, you may be able to improve the course of the disorder.
CALD, also called childhood CALD, is a rare progressive neurological disorder. It’s the most severe type of adrenoleukodystrophy (ALD).
CALD results from a mutation in the ABCD1 gene, which is present on the X chromosome. People with CALD have a buildup of very-long-chain fatty acids (VLCFAs) in their brain and nervous system. VLCFAs destroy the protective fatty layer around nerves called myelin, which can lead to a rapid loss of motor and cognitive abilities in early childhood.
The outlook for CALD remains poor, and most children pass away within the first decade of their life. Receiving prompt treatment with a stem cell transplant or gene therapy may improve the course of the disorder, if treatment begins before neurological symptoms develop.
In this article, we examine CALD in more detail, including what causes it and how to manage it.
How common is CALD?
Experts think ALD occurs in about 1 in 17,000 live births. They believe around
It occurs almost exclusively in males, though females may develop milder symptoms later in life.
CALD is a severe type of ALD resulting from a recessive mutation in the ABCD1 gene, which is present on your child’s X chromosome. Males only have one X sex chromosome, but females have a backup copy. CALD primarily occurs in young males.
Females with ALD tend to have milder symptoms and rarely have cognitive dysfunction. Only
Experts believe ALD is most common in people of
Doctors usually diagnose CALD in early childhood, but they can also diagnose it before birth by using a needle to take a sample of the amniotic fluid or placenta.
Children with CALD typically develop normally until the ages of 3 to 10 years, then they may begin developing symptoms.
The first symptom of CALD is often behavioral or academic decline, which doctors sometimes misdiagnose as attention deficit hyperactivity disorder (ADHD).
It typically progresses with:
- vision and hearing loss
- trouble walking
- loss of bladder control or bowel control
- bulbar dysfunction, which may cause:
- lip trembling
- drooling
- vocal cord paralysis
- throat muscle weakness
- trouble chewing
- seizures
As the disorder progresses even further, your child may develop additional symptoms, such as:
Doctors in most states now routinely screen newborns for CALD at birth by taking a drop of blood.
They can also diagnose CALD later in childhood once characteristic signs and symptoms develop. If your child’s doctor suspects CALD, they may order a blood test to look for characteristic features, such as:
- increased VLCFA concentration
- an associated gene mutation
- increased concentration of pipecolic and phytanic acid
MRI also plays an
After diagnosis, your child will likely need to have repeated MRIs to track brain changes over time. CALD treatment needs to begin as quickly as possible to improve the course of the disorder.
CALD isn’t currently curable, but the course of the disorder is usually better with treatment. Without treatment, CALD often progresses to a vegetative state and death within about 2 to 3 years from the onset of neurological symptoms. Most children pass away within the first decade of their life.
The following are some treatments available for CALD.
Hematopoietic stem cell transplant
Hematopoietic stem cell transplant (HSCT) has emerged as a potential treatment option for children who don’t yet have neurological symptoms. However, in about half of children, doctors diagnose the disorder too late to see a benefit from this treatment.
HSCT involves infusing hematopoietic stem cells from a donor into your child’s bloodstream. These cells are present inside of bone marrow, and they create new blood cells.
HSCT may stop the progression of neurological disease, but it can’t reverse neurological damage once it occurs.
In a small 2023 study from France, researchers found that
Supportive treatment options
Supportive treatment can improve your child’s comfort and maximize their quality of life. Supportive
- breathing support
- pain relief medications
- feeding support
- speech therapy
- physical therapy or occupational therapy
- corticosteroid replacement therapy
- palliative care
Gene therapy
The Food and Drug Administration (FDA) approved Skysona, the first gene therapy for treating CALD, in the United States in 2022.
Skysona slows the progression of active CALD in boys ages 4 to 17 years. This medication involves infusing a working copy of the ABCD1 gene into stem cells removed from your child’s body. A doctor then infuses the stem cells back into your child’s bloodstream to start producing the missing protein that leads to the buildup of VLCFAs.
In one of the clinical trials that led to Skysona’s approval, researchers found that children who received treatment with Skysona had better survival at 24 months than children who didn’t. Children who received Skysona had a 72% major disability-free survival at 24 months compared with 43% in children who didn’t.
Despite Skysona potentially being effective, experts have linked it to the development of blood cancer as soon as
Resources for CALD
Here are some resources for families affected by ALD and CALD:
- Find clinical trials for CALD from the National Library of Medicine.
- Download a Parent Guide from the ALD Alliance.
- Find a list of support groups from the ALD Alliance.
- Find further resources from Navigating ALD.
CALD is a rare genetic disorder that causes degeneration of the nervous system early in childhood. Untreated CALD has a poor outlook and often leads to death before the age of 10 years.
Research suggests that receiving a stem cell transplant and gene therapy before neurological symptoms develop may improve the course of the disorder. Doctors in many states are now routinely testing for CALD in newborns so that they can begin treatment as soon as possible.