ALD, or adrenoleukodystrophy, is a rare genetic disorder in which the body cannot properly break down certain fats called very long-chain fatty acids (VLCFAs). These fats build up in the brain, spinal cord, and adrenal glands, damaging the protective coating around nerve fibers and disrupting hormone production. The condition is X-linked, meaning the gene responsible sits on the X chromosome, so it primarily affects boys and men, though women who carry the gene can also develop symptoms.
What Happens in the Body
Every cell has small structures called peroxisomes that help break down fats. A protein called ABCD1 acts as a gateway, pulling long-chain fats into the peroxisome so they can be chopped into smaller, usable pieces. In ALD, mutations in the gene that makes this protein prevent those fats from entering the peroxisome. Over 800 different mutations in this gene have been identified.
When these fats can’t be broken down, they accumulate throughout the body, particularly in the brain and adrenal glands. In the brain, they damage myelin, the insulating sheath that allows nerve signals to travel quickly and efficiently. As myelin breaks down, neurological function deteriorates. In the adrenal glands, the buildup impairs the production of cortisol and other essential hormones.
The Three Main Forms
ALD doesn’t look the same in every person. It has three primary forms, categorized by which organs are affected and when symptoms appear.
Childhood Cerebral ALD
This is the most severe form. Boys typically develop normally as infants and toddlers, then begin losing skills between ages 3 and 10. Early signs often look like behavioral or attention problems: difficulty focusing in school, trouble with reading or handwriting, and episodes of “spacing out” that can be mistaken for ADHD or learning disabilities. The key difference is regression. Rather than struggling to learn new skills, these children lose abilities they already had.
As the disease progresses, children develop vision problems and seizures. The decline is often rapid, and without treatment, children with this form typically pass away within a few years of the first neurological symptoms appearing.
Adrenomyeloneuropathy (AMN)
This is the most common form in adults. Symptoms usually begin in the late twenties for men and after menopause for women. Rather than attacking the brain’s white matter like the childhood form, AMN primarily damages the spinal cord. The result is progressive stiffness and weakness in the legs, difficulty walking, balance problems, bladder and bowel control issues, and sexual dysfunction. Some people with AMN also develop brain involvement over time, which can cause behavioral changes, vision loss, and hearing problems.
Most men with ALD who survive into adulthood have this form. About 65% of women who carry the gene mutation will develop some degree of symptoms by age 65, though their symptoms tend to be milder or appear later than in men.
Adrenal Insufficiency (Addison’s Disease)
Some people with ALD develop problems only in their adrenal glands, without obvious neurological symptoms. The adrenal glands stop producing enough cortisol and aldosterone, hormones that regulate energy, blood pressure, and salt balance. This causes chronic fatigue, low blood pressure, dehydration, low blood sugar, and general weakness. Darkening of the skin is another telltale sign. Males with ALD have an 80% lifetime risk of developing some degree of adrenal insufficiency, regardless of which form they have.
How ALD Is Diagnosed
The first step is a blood test measuring levels of very long-chain fatty acids. Elevated levels are a strong indicator, though the test is sensitive rather than specific, meaning other conditions can also raise these fat levels. Genetic testing to confirm the ABCD1 mutation is needed for a definitive diagnosis.
For the cerebral form, brain MRI plays a critical role. Doctors use a scoring system called the Loes score, which rates the extent and location of white matter damage in the brain. This score helps predict how the disease will progress and, critically, helps determine the right timing for treatment. Regular MRI monitoring is essential for boys known to carry the gene, even before any symptoms appear.
ALD is now on the Recommended Uniform Screening Panel (RUSP) for newborn screening in the United States, which means most states either screen for it at birth or are in the process of adopting screening. This has been a significant shift, because early detection before symptoms appear opens the door to treatments that can change outcomes dramatically.
Treatment Options
Timing is everything with ALD treatment. The most effective interventions work only when the disease is caught early, before significant brain damage has occurred.
Stem Cell Transplant
Hematopoietic stem cell transplant (from a donor’s bone marrow or blood) is the standard treatment for boys with early cerebral ALD. The transplanted cells produce working copies of the ABCD1 protein, which can halt the progression of brain damage. A study comparing treated and untreated boys found that five-year survival was 78% for those who received a transplant, compared to 55% for those who did not. Among boys treated very early, with low Loes scores and minimal brain involvement, two-year survival without major functional disability reached 84%.
The catch is that the transplant works best when brain involvement is minimal. Once significant damage has occurred, the procedure becomes less effective and carries higher risk. This is why newborn screening and regular MRI monitoring matter so much.
Gene Therapy
For boys aged 4 to 17 with early, active cerebral ALD who don’t have a matched stem cell donor available, the FDA has approved a gene therapy called Skysona. Instead of using donor cells, this approach takes the patient’s own stem cells, inserts a working copy of the ABCD1 gene, and infuses them back. The goal is the same: slow the progression of neurological damage.
Managing Adrenal Insufficiency
Because adrenal problems are so common in ALD, hormone replacement is a lifelong need for many patients. Replacing cortisol and other adrenal hormones prevents the fatigue, low blood pressure, and metabolic problems caused by adrenal insufficiency. This treatment doesn’t address the neurological aspects of the disease but is essential for daily health and can be lifesaving during physical stress like illness or surgery.
Lorenzo’s Oil
Lorenzo’s oil, a dietary supplement made from olive oil and rapeseed oil, gained attention after the 1992 film about the family who developed it. The oil can normalize blood levels of very long-chain fatty acids within about four weeks. However, whether lowering blood levels actually prevents or slows neurological disease remains unclear. Without placebo-controlled studies, a definitive conclusion about its effectiveness hasn’t been reached. It is sometimes used in asymptomatic boys alongside monitoring, but it is not considered a substitute for transplant or gene therapy once brain involvement begins.
How ALD Affects Women
Because ALD is X-linked, women who carry one copy of the mutated gene have a second, working copy on their other X chromosome. This generally provides some protection, but it’s not complete. Women carriers can develop symptoms similar to AMN, including leg stiffness, weakness, balance problems, and bladder issues. These symptoms typically appear later in life, often after menopause, and tend to progress more slowly than in men. Adrenal insufficiency is much less common in women carriers than in men.