Adrenoleukodystrophy: A genetic disease that affects the nervous system

Adrenoleukodystrophy (ALD) is a rare genetic disorder that affects the nervous system and the adrenal glands. This condition is caused by a mutation in the ABCD1 gene, which interferes with the body’s ability to break down certain very long-chain fatty acids. As a result, these fatty acids accumulate in the brain and other parts of the body, causing progressive damage to the myelin (the protective layer around neurons) and hormonal imbalances. ALD can present in various forms, and symptoms vary depending on the age of onset and the predominant type of involvement.

What is Adrenoleukodystrophy?

Adrenoleukodystrophy (ALD) is an X-linked hereditary disorder that primarily affects males, although carrier females may also develop symptoms later in life. There are different types of ALD:

1. Childhood cerebral ALD: This is the most severe form and appears in boys between the ages of 4 and 10. It rapidly causes neurological degeneration and can lead to death within a few years if left untreated.
2. Adrenomyeloneuropathy (AMN): This type mainly affects young adult males and leads to progressive motor problems in the legs and muscle weakness.
3. Adrenal insufficiency (Addison’s disease): Involvement of the adrenal glands causes hormone deficiency, leading to symptoms such as fatigue, weight loss, and low blood pressure.
4. ALD in female carriers: Although female carriers typically do not develop the cerebral form of the disease, they may experience AMN-like symptoms in adulthood.

Causes of Adrenoleukodystrophy

ALD is caused by a mutation in the ABCD1 gene, located on the X chromosome. This gene is responsible for encoding a protein that transports very long-chain fatty acids into peroxisomes, where they are supposed to be broken down. In individuals with ALD, this function is impaired, leading to the accumulation of fatty acids in the tissues of the nervous system and the adrenal glands.

As these fatty acids accumulate, they damage the myelin, the substance that surrounds nerve fibers and enables proper transmission of electrical impulses in the nervous system. This progressive damage to the myelin is responsible for the characteristic neurological symptoms of ALD.

Symptoms of Adrenoleukodystrophy

The symptoms of ALD can vary depending on the form of the disease and the age of onset. Some of the most common symptoms include:

• Attention and behavior problems: Children with childhood ALD may show changes in behavior and have difficulty concentrating on school tasks.
• Cognitive and neurological decline: Progressive loss of motor skills, mental deterioration, and difficulty speaking are common in the more severe forms of ALD.
• Muscle weakness and coordination issues: Individuals with adrenomyeloneuropathy may experience muscle stiffness, difficulty walking, and spasms.
• Adrenal insufficiency: Fatigue, weight loss, and low blood pressure are common in patients who develop adrenal insufficiency.

Since ALD can affect the brain, spinal cord, and adrenal glands, the severity and course of the disease are extremely variable, even among members of the same family.

Diagnosis of Adrenoleukodystrophy

The diagnosis of ALD involves a combination of laboratory tests and imaging studies. Some of the most common tests include:

Treatment of Adrenoleukodystrophy

The treatment of ALD is complex and depends on the specific form and severity of the disease. Current treatment options include:

1. Hormone replacement therapy: In cases of adrenal insufficiency, treatment with corticosteroids helps replace the hormones the body can no longer produce properly.
2. Hematopoietic stem cell transplant: This treatment is most effective in the early stages of childhood cerebral ALD and can stop or slow the progression of the disease.
3. Lorenzo’s oil: This blend of special fatty acids has been shown to reduce the accumulation of very long-chain fatty acids, although its effectiveness in preventing neurological symptoms is limited.
4. Physical and occupational therapy: Rehabilitation helps improve the quality of life for patients with AMN by providing support for mobility and daily functioning.

Current research is exploring new alternatives such as gene therapy, which could correct the mutation in the ABCD1 gene and prevent the accumulation of fatty acids. This area of research is promising, although it is still in the early stages.

Prevention and Management of Adrenoleukodystrophy

Although there is no definitive way to prevent ALD due to its genetic origin, genetic testing can help identify carriers and support informed family planning decisions. In addition, early detection in individuals at high risk (such as sons of carrier mothers) allows for proactive management, including monitoring of adrenal function and neurological follow-up.

Early intervention and a multidisciplinary approach are essential for managing symptoms and improving patients’ quality of life. Support programs and genetic counseling are also very helpful for affected families.

Conclusion

Adrenoleukodystrophy (ALD) is a serious and debilitating genetic disorder that affects the nervous system and adrenal glands. It can present in various forms, ranging from neurological deterioration in childhood to adrenal insufficiency in adulthood. The accumulation of very long-chain fatty acids, caused by a mutation in the ABCD1 gene, is the main trigger of this condition. Early diagnosis and specialized treatment are essential to prevent or slow its progression.

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