Adrenoleukodystrophy

Adrenoleukodystrophy (ALD) is a genetic condition that harms the protective covering (myelin sheath) around nerve cells in the brain. This protective covering is crucial for healthy nerve signals.

In ALD, the body has trouble breaking down certain fats called very long-chain fatty acids (VLCFAs). When this happens, these fats build up in the brain, nerves, and adrenal glands, causing damage.

The most common type of ALD is X-linked ALD. This means the faulty gene that causes the problem is located on the X chromosome. Because females have two X chromosomes, they often have one healthy copy of the gene, which can protect them from the most severe effects. Males, however, only have one X chromosome, so if they inherit the faulty gene, they are more likely to develop the condition.

X-linked ALD comes in different forms, each with its own set of symptoms and severity:

• Childhood-onset ALD: This type usually appears between the ages of 4 and 10. The condition gradually damages the brain's white matter (leukodystrophy), leading to worsening symptoms. Without early diagnosis and treatment, childhood-onset ALD can be fatal within 5 to 10 years. This means the child's brain function gets progressively worse, eventually leading to serious problems.

• Addison's disease: The adrenal glands, which produce important hormones, often don't function properly in people with ALD. This reduced hormone production (adrenal insufficiency) is a type of X-linked ALD, and is sometimes called Addison's disease. Without enough hormones, the body can't function normally.

• Adrenomyeloneuropathy: This form of ALD appears later in life, usually in adulthood. It's less severe than childhood-onset ALD and progresses more slowly. Symptoms can include difficulty walking (stiff gait), problems with bladder and bowel control, and other nerve-related issues. Women who carry the faulty gene might experience a milder form of this type of ALD.

Diagnosing adrenoleukodystrophy (ALD) involves a thorough evaluation by your doctor. They'll start by asking about your symptoms and your medical history, including your family's health. A physical exam is also part of the process. Several tests are commonly ordered:

1. MRI (Magnetic Resonance Imaging): An MRI uses powerful magnets and radio waves to create detailed pictures of your brain. These images help doctors look for any unusual changes that might be signs of ALD, such as damage to the white matter in your brain. Different types of MRI scans can provide different views of the brain, helping to spot early signs of the disease.

2. Vision Screening: This test measures how your eyes respond to light. It can help track the progression of ALD, especially in males who don't yet have noticeable symptoms.

3. Skin Biopsy and Fibroblast Cell Culture: Sometimes, a small skin sample is taken. This sample is then grown in a lab (fibroblast cell culture). The lab tests the cells for higher-than-normal levels of very long-chain fatty acids (VLCFAs). High levels of VLCFAs can be a sign of ALD.

4. Blood Tests: Blood tests are crucial for diagnosing ALD. They check for high levels of VLCFAs in the blood. High VLCFAs are a strong indicator of the disease. Blood tests also help evaluate how well your adrenal glands are functioning. Additionally, blood samples are used for genetic testing. This testing looks for specific gene defects or changes that cause ALD.