Adrenoleukodystrophy – Symptoms and Causes

Overview

Adrenoleukodystrophy (ALD) is a genetic disorder that damages the protective coating around nerve cells in the brain.

This condition prevents the body from breaking down very long-chain fatty acids (VLCFAs), which then accumulate in the brain, nervous system, and adrenal glands.

X-linked ALD is the most common form, caused by a genetic defect on the X chromosome. This type affects males more severely, while females typically act as carriers of the disease.

Symptoms

Adrenoleukodystrophy (ALD) affects people differently based on the type and when it develops. Signs often appear between ages 4 and 10 in childhood cerebral ALD.

Early symptoms may include:

• Behavioral changes like withdrawal or attention problems
• Memory issues and declining school performance
• Vision and hearing problems
• Poor coordination or difficulty walking
• Seizures
• Trouble swallowing

In adrenomyeloneuropathy (AMN), the adult form, symptoms typically begin in the late 20s or 30s and include:

• Stiffness in the legs
• Progressive weakness in the legs
• Changes in walking pattern
• Urinary and bowel control problems

Many people with ALD develop adrenal insufficiency (Addison’s disease), which can cause:

• Weakness
• Fatigue
• Skin darkening
• Weight loss
• Vomiting
• Low blood pressure

Women who carry the ALD gene may experience milder symptoms similar to AMN, usually starting after age 35.

Causes

Adrenoleukodystrophy (ALD) occurs due to genetic mutations in the ABCD1 gene. This gene provides instructions for making a protein that helps break down very long-chain fatty acids (VLCFAs).

When the gene is faulty, these fatty acids build up in the body and damage the protective covering of nerve cells in the brain and spinal cord.

ALD is inherited in an X-linked pattern, which means the defective gene is located on the X chromosome. Males have only one X chromosome, so one altered copy of the gene causes the condition.

Females have two X chromosomes, so a mutation would need to occur in both copies to cause severe symptoms.

Several factors can affect how ALD develops:

• Genetic Inheritance: Most people with ALD inherit the gene mutation from a parent.
• Spontaneous Mutations: In rare cases, the mutation occurs randomly without being inherited.
• Age and Gender: Different forms of ALD appear at different ages, with males usually experiencing more severe symptoms.

The buildup of VLCFAs damages the adrenal glands and myelin sheath (the protective covering around nerve cells). This damage leads to the neurological and hormonal problems seen in people with ALD.

Environmental factors don’t cause ALD, but they might influence when symptoms appear or how quickly the disease progresses. Research continues to explore what triggers symptom onset in people who carry the genetic mutation.

Risk Factors

Several factors may increase the chance of developing or experiencing adrenoleukodystrophy (ALD). The most significant risk factor is having a family history of the disorder.

Since ALD is inherited through an X-linked pattern, males with the genetic mutation will develop some form of the condition.

Women who carry the genetic mutation have a 50% chance of passing it to each of their children. Males who inherit the mutation will develop symptoms, while females typically become carriers, though they may experience milder symptoms later in life.

Age plays an important role in how ALD presents. Childhood cerebral ALD typically appears between ages 4-10, while adrenomyeloneuropathy usually develops in adulthood, often between ages 20-40.

Genetic Testing Considerations:

• Family members of affected individuals
• Males with unexplained neurological symptoms
• Females with unexplained adrenal insufficiency

Environmental factors don’t cause ALD, but they may potentially influence how quickly symptoms progress in people who have the genetic mutation.

Stress and illness might trigger or worsen symptoms in those with the condition, particularly related to adrenal function.

Complications

Adrenoleukodystrophy (ALD) can lead to serious health problems as it progresses. When left untreated, the disease may cause permanent disability and even death in severe cases.

Brain damage from ALD often results in cognitive decline. Patients might experience memory problems, difficulty processing information, and decreased mental function.

These changes can affect school performance in children or work capability in adults.

Physical disabilities frequently develop as the disease advances. Many patients experience:

• Muscle weakness or paralysis
• Problems with coordination
• Difficulty walking
• Loss of ability to speak clearly

Vision and hearing loss can occur as the disease damages nerve pathways. Some patients may become completely blind or deaf as ALD progresses.

Adrenal insufficiency creates additional health risks. Without proper hormone production, the body struggles to manage stress, maintain blood pressure, and regulate blood sugar.

This can lead to a life-threatening adrenal crisis during times of illness or stress.

Seizures develop in approximately 30-40% of patients with cerebral ALD. These episodes may be difficult to control with standard medications and can cause further brain damage.

Behavioral and emotional problems often accompany ALD. Patients might display aggression, depression, or personality changes that disrupt family dynamics and social relationships.

Infections become more common and dangerous as the disease progresses. Weakened immune function and decreased mobility make patients vulnerable to pneumonia and other serious illnesses.