Pediatric adrenoleukodystrophy (ALD)

What is pediatric adrenoleukodystrophy (ALD)?

ALD, or X-linked ALD, stems from a disease-causing (pathogenic) variant in the ABCD1 gene. This variant disrupts how the body processes fatty acids, causing them to build up in the brain and adrenal glands (glands that sit on top of the kidneys).

Left unchecked, ALD can lead to adrenal insufficiency – the inability to make important hormones that regulate our metabolism, blood pressure and how we respond to stress. It can also lead to damage to the protective myelin sheath around nerves, which affects movement, behavior and development.

What are the different types of pediatric adrenoleukodystrophy (ALD)?

There are four types of X-linked adrenoleukodystrophy:

• Cerebral ALD (CALD): This is the most serious form, with symptoms typically appearing between ages 4 to 6 (and sometimes as early as age 2). Without treatment, progression leads to loss of walking, speech, and severe neurological decline. About 30 to 40% of boys with ALD will develop this type.

• Adrenal Insufficiency: This happens when the adrenal glands don’t produce enough hormones. About 80 to 90% of boys with ALD will have adrenal insufficiency, which requires life‑saving hormone replacement medications.

• Adrenomyelopathy (AMN): This later-onset form affects nerve function and is generally seen in adulthood – in both men and women. It typically causes stiffness and weakness and possibly cognitive decline.

• Asymptomatic variant carriers: Some people identified through genetic testing may show no signs or symptoms of the disease for years. When symptoms appear later in life, they’re typically milder.

Why early, active surveillance for ALD matters

Right now, there is no way to predict what kind of ALD disease a child will develop – and the goal is always to prevent the most severe, cerebral form. And because a child can appear healthy but still be experiencing damaging changes to their brain, the only way to detect signs of the disease affecting the brain is through regular brain magnetic resonance imaging tests (MRIs).

Finding changes to a child’s brain early is very important because there is a narrow “treatment window” for kids who develop the cerebral form. Once a child shows significant damage to their brain, there are no longer any treatment options. But when changes are found early, treatment can go a long way towards preventing the progression of the disease – giving your child a good chance at living a longer, healthier life.

What are the signs and symptoms of pediatric adrenoleukodystrophy (ALD)?

Many kids experience damage to their brain or adrenal glands before they show symptoms of ALD.

Symptoms for children who develop the cerebral form of X-ALD or adrenomyelopathy (AMN) can include:

• Behavior problems (including aggressive behavior)

• Difficulty walking and poor coordination

• Difficulty speaking, reading and writing

• Memory problems

• Hearing and vision problems

• Bladder problems

• Difficulty swallowing

• Hypertonia (excessive muscle tone)

• Nausea or vomiting

• Seizures

• Weight loss

Symptoms of adrenal insufficiency include:

• Darkening of the skin (hyperpigmentation)

• Decreased appetite and weight loss

• Feeling tired

• Feeling irritable or depressed

• Muscle or joint pain

• Pain in the abdomen, lower back or legs

• Nausea or vomiting

• Craving salt or salty foods (hyponatremia), due to low sodium levels

• Fainting due to low blood pressure (hypotension)

• High potassium (hyperkalemia)

• Low blood sugar (hypoglycemia)

How is pediatric adrenoleukodystrophy (ALD) diagnosed?

The disease-causing genetic variant or the disease itself can be found in a few ways:

• Newborn screening. ALD is often found at birth through newborn screening programs in certain states, including Texas. Newborn screening helps you get on a path of active surveillance as soon as possible, which is key to keeping your child as healthy as possible.

• Sibling/family screening. When we find one child with the genetic variant in a family, our genetic specialists also test other family members for the variant.

• When symptoms appear. If screening wasn’t available, ALD may also be diagnosed after a child begins to show symptoms, which is often around age 4.

What causes pediatric adrenoleukodystrophy (ALD)?

Adrenoleukodystrophy is caused by a gene mutation on the X chromosome of the ABCD1 gene, which is sometimes passed on from a mother to her child. This genetic mutation causes fatty acids to build up in the brain, nervous system and adrenal glands.

How is pediatric adrenoleukodystrophy (ALD) treated?

From the moment you find out your child has the genetic variant, our team is here for you. Your doctor can call and speak to one of our genetic counselors who cover newborn screening sand help get you scheduled for an appointment, usually within a few days. At your first appointment, we’ll walk you through what you can expect and get you connected to our pediatric endocrinologists and neurologists that specialize in ALD.

Our goal is to help you understand the importance of being proactive in the treatment of ALD – and of actively monitoring your child for signs of ALD through regular MRIs and blood tests.

Treatments for X-ALD include:

Gene therapy

The gene therapy Skysona is a one-time, FDA-approved treatment for kids with CALD. Since it was approved in 2022, Skysona has proven to significantly slow the progression of damage to a child’s brain and nervous system. Children’s Health is one of only a few centers worldwide to offer this gene therapy for children with CALD who meet the treatment requirements. Treatment with Skysona uses a child’s own stem cells – so there’s no need to wait for a donor match.

Stem cell transplant

Stem cell transplant can slow or stop the progression of the cerebral form of ALD – if it’s done when an MRI first shows signs of the disorder. Stem cell transplant requires finding a donor match in the bone marrow registry or from a family member. Our team of pediatric hematologists/oncologists at our world-class Pauline Allen Gill Center for Cancer and Blood Disorders have special expertise performing stem cell transplants for kids. Every year, we perform dozens of stem cell transplants in kids ranging from 1-month-old to 21 years of age.

About one-third to half of kids diagnosed who develop the cerebral form of ALD will need either a stem cell transplant or gene therapy. If your child needs one of these treatments, our team will walk you through the pros, cons and risks of each option – plus the preparation and recovery process. Our aim is always to help you make the best decision for your child and your family.

Hormone replacement medications

For children with primary adrenal insufficiency, our endocrinologists with special expertise in treating kids with ALD will prescribe hydrocortisone or fludrocortisone to replace and monitor critical hormone levels.

Supportive therapies and medications

Depending on a child’s symptoms, physical therapy, occupational therapy and speech therapy can help improve their function and quality of life. We can also manage kids who experience seizures or spasms with medications.

Hydrocortisone injection video

This injection should be used when your child cannot take Hydrocortisone or Prednisone by mouth due to vomiting or unconsciousness. Please utilize this video as a periodic refresher so that if or when you need to give this injection you feel comfortable doing so. After administering Solu-Cortef, you should call 911 or call our office at 214-456-5959. Learn more about hydrocortisone injections in children.

• Medline Plus: X-linked adrenoleukodystrophy

• Stop ALD Foundation

• ALD Alliance, formerly known as the Aidan Jack Seeger Foundation

• ALD Connect

• United Leukodystrophy Foundation