Causes of adrenoleukodystrophy 

ALD is a rare genetic condition caused by mutations in the gene that prevents the body from transporting very-long-chain fatty acids (VLCFAs) into the part of the cell that breaks them down (peroxisomes). As a result, VLCFAs build up in the blood, brain, nervous system and adrenal glands. In some patients, the body responds by destroying the protective myelin sheath around the brain’s nerve cells. While it is not understood what triggers ALD to become CALD, it is estimated that this occurs in less than 30% of affected children.

Signs and symptoms of pediatric CALD

Symptoms of CALD usually begin around ages 4 to 8 in a percentage of boys affected by ALD. Symptoms include:  

• behavioral or learning deficits 
• deterioration in handwriting skills 
• poor school performance 
• difficulty understanding speech 
• difficulty reading 
• clumsiness 

As the disease progresses, symptoms include visual disturbances, loss of hearing, seizures, and trouble moving or speaking, eventually leading to loss of all body functions over a few years. 

Testing and diagnosis for pediatric CALD

Early diagnosis and treatment are crucial for better chances of slowing the progression of CALD. Some states have added adrenoleukodystrophy to their newborn screening. The newborn screening is a series of special tests that check a baby for health conditions at birth.

Early diagnosis through the newborn screening is helpful in identifying children at risk for ALD, but it can't predict which form of the condition — adrenal, cerebral or adult AMN— a child will have, or when the symptoms will start to impact them, if at all. This is why it is so important for boys affected by ALD and their family members to receive care in a specialized center. 

Treatment for pediatric CALD

Currently, there is no complete cure for ALD, but there are treatments that significantly change the course of this disease. The following treatments are available: 

Stem cell transplant 

Stem cell transplant may stop or slow the progression of CALD if it is done when neurological signs first appear on a specialized image of the brain called an MRI. Stem cell transplantation (also called a bone marrow transplant) requires a match in the bone marrow registry or from a matched family member.  

Gene therapy

Gene therapy offers an alternative to stem cell transplant. Elivaldogene autotemcel (brand name: Skysona®) is a one-time, ex vivo gene therapy that slows the progression of neurologic dysfunction. For the treatment, stem cells are taken out of a child’s body, treated with the healthy gene they need, and then reinfused back into their body. A bone marrow match, which can be difficult to find for some patients, is not needed because the body’s own cells are used for the transplant. 

CHOP is one of the few centers in the world able to offer this CALD treatment option.  

Medications

Doctors may prescribe medications to help relieve symptoms such as stiffness and seizures. Close follow-up with a neurologist and or rehabilitation medicine physician is helpful. 

Physical therapy 

Physical therapy may help relieve muscle spasms and reduce muscle rigidity. 

Adrenal insufficiency treatment

Many children with ALD develop adrenal insufficiency, which can be effectively treated with steroids. Adrenal insufficiency can be life threatening without treatment. Close follow-up with a doctor specialized in hormone therapy, or an endocrinologist, is helpful. 

Follow-up Care 

Every child identified with ALD through the newborn screening must receive standardized neurologic monitoring throughout childhood that includes blood work and brain MRIs. This allows clinicians to see changes in the brain before the child shows any physical symptoms. This also allows treatment of adrenal insufficiency, which can be life threatening. If the care team sees anything concerning, they can provide personalized intervention immediately before a child has permanent injury to their brain. Targeted treatment of CALD has the best outcome when performed on an individual before symptoms are clinically visible. 

Long-term outlook

Historically, hematopoietic stem cell transplantation (bone marrow transplant) was the only targeted treatment option available to prevent the progression of CALD. However, stem cell transplantation requires a match in the bone marrow registry. For many children, a good donor match doesn’t exist. 

The gene therapy recently approved by the U.S. Food and Drug Administration (FDA) — noted above — offers an alternative treatment. It uses a child’s own stem cells, so it doesn’t require a match in the registry. 

In recent clinical trials, gene therapy has shown promising results in stabilizing the progression of the disease in boys with early-stage CALD. However, additional research is necessary to assess its long-term effectiveness and safety.