ALD Connect

What is ALD?

Adrenoleukodystrophy (ALD) is a progressive, genetic disease that affects the adrenal glands, the spinal cord, and the white matter (myelin) of the nervous system. ALD is considered a rare disease, and affects approximately 1 in 17,000 people worldwide.

About ALD

Adrenoleukodystrophy (ALD) is a rare, genetic disorder that primarily affects the nervous system and adrenal glands. It is an X-linked disease that is caused by mutations in the ABCD1 gene, which affects the body’s ability to create the protein that helps break down very long–chain fatty acids (VLCFAs). This accumulation of VLCFAs can result in a range of symptoms, from adrenal insufficiency to severe neurological dysfunction. ALD can manifest differently depending on the age and sex of the individual, making early diagnosis and ongoing monitoring crucial for managing the disease.

WHAT IS ALD? Adrenoleukodystrophy explained.

What are the symptoms of ALD?

The symptoms of adrenoleukodystrophy (ALD) vary based on the specific type and the age and sex of the individual. Adrenal insufficiency, characterized by fatigue, muscle weakness, low blood pressure, and skin darkening, is common in both children and adults with ALD. Boys and men with cerebral ALD experience neurological decline, including behavioral changes, vision loss, difficulty with coordination, and cognitive impairment. In adult males, ALD often presents as adrenomyeloneuropathy (AMN), causing stiffness, weakness in the legs, pain, and bladder or bowel dysfunction. Women with ALD may experience neurological symptoms, similar to those experienced by men with AMN. Because ALD affects the nervous system and adrenal glands differently in each person, symptoms can range from mild to severe and may evolve over time.

How does ALD progress over time?

In medical terms, a collection of symptoms is known as a “phenotype.” Individuals with the ALD gene mutation may exhibit different phenotypes over their lifetime, reflecting the disorder’s varied progression. Some people may develop multiple phenotypes concurrently, while others might remain symptom-free for extended periods. It’s important to note that the expression of symptoms can differ greatly, making early diagnosis and ongoing monitoring essential.

The primary phenotypes that can occur in individuals with the ALD gene mutation are listed below. Click each link to learn more about the specific phenotype.

ALD Phenotypes

Asymptomatic (Newborn Screening)

If someone with ALD is asymptomatic, it means they do not currently show any signs or symptoms of the disorder. Babies identified through newborn screening fall into this category. Most individuals with the ALD gene mutation remain symptom-free for at least the first few years of life.

Some may not develop symptoms for many years; however, the percentage of asymptomatic men and women decreases with age. Regular monitoring is especially crucial for asymptomatic boys, as they are at risk of developing serious complications such as adrenal insufficiency and cerebral ALD.

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ALD Phenotypes

Adrenal Insufficiency

Adrenal insufficiency (AI) is a common and early complication in boys with adrenoleukodystrophy (ALD). This condition arises due to the progressive damage to the adrenal glands, which impairs their ability to produce essential hormones like cortisol.

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ALD Phenotypes

Cerebral ALD

Childhood cerebral ALD is the most severe form of adrenoleukodystrophy (ALD). It is characterized by an inflammatory process that destroys the brain’s myelin, the protective coating of nerve cells that facilitates rapid transmission of information. The progressive deterioration of myelin in cerebral ALD is relentless and can lead to significant neurological impairment if not detected and treated early.

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ALD Phenotypes

Adrenomyeloneuropathy (AMN)

Adrenomyeloneuropathy (AMN) is the most common form of adrenoleukodystrophy (ALD). It affects adult men, typically presenting with a gradual onset of stiffness and weakness in the legs, difficulty with walking, and pain or discomfort due to nerve damage. Unlike cerebral ALD, AMN progresses more slowly and does not usually involve severe cognitive decline, but it can lead to significant disability over time.

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ALD Phenotypes

(A)Symptomatic Women with ALD

Most women with a genetic mutation in the ABCD1 gene will develop myeloneuropathy in adulthood, with an average age of symptom onset of around 40 years of age. Symptoms similar to those in men with AMN are common, including gait disturbances, pain, and bowel and bladder dysfunction. In recognition that women are not just “carriers” of the disease but are ALD patients themselves, a group of international ALD experts recommends referring to female patients as “asymptomatic /presymptomatic” or “symptomatic women with ALD” instead of terms such as “heterozygotes” or “carriers”.

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