What is adrenoleukodystrophy?

Adrenoleukodystrophy (ALD) is a rare X-linked genetic disorder that affects the brain and adrenal glands (small glands that produce important hormones in the body). This condition causes accumulation of harmful fatty acids in the blood stream, resulting in damage to myelin in the brain and spinal cord, as well as the adrenal glands. Myelin is the insulation around our nerves. The nervous system needs myelin to function properly.

ALD can be diagnosed at birth through newborn screening programs or when a patient or family member begins to show symptoms. Affected newborns are typically healthy for many years, and some may never show symptoms of disease.

There are a few different forms of ALD:

• Cerebral-ALD – The most serious form of ALD is cerebral-ALD, or CALD. Symptoms usually begin in early childhood and manifest with changes to behavior, seizures or motor skills. Without treatment, children can lose their ability to move and think. Untreated, CALD eventually causes profound loss of skills or death within a few years of showing symptoms. This condition only affects boys and is not seen in female carriers.
• Adrenal insufficiency – Children with ALD can also present with adrenal insufficiency. The adrenal gland is important as it makes hormones (for example cortisol) that help the body respond to stress, in addition to other things. Children can present with changes in skin color, low blood pressure, and severe responses to situations like an infection. This condition typically affects boys.
• Adrenomyeloneuropathy – Adults may present with changes in their spinal cord over time, a condition called adrenomyeloneuropathy (AMN). This condition can affect men or carrier women.

Causes of adrenoleukodystrophy

ALD is a rare genetic condition caused by genetic variants in the ABCD1 gene, which prevent 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, this build up leads to damage of the protective myelin sheath around the brain’s nerve fibers. While it is not understood what triggers ALD to become CALD, it is estimated that this occurs in less than 30 percent 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. 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.

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.

 

ABOUT THE ARMER FOUNDATION FOR KIDS:
Founded by Jennifer and Matt Armer in 2019, the Armer Foundation For Kids (a 501(c)(3) 84-2327428) works to reduce
financial barriers for families so that they can care for their children with chronic or life-altering diseases that can often
lead to unforeseen financial burdens. For more information and to see the children for which they are currently
fundraising, visit www.armerfoundation.org.