Blog
Adrenoleukodystrophy (ALD)
Covenant Metabolic Specialists Health Library
Covenant Metabolic Specialists
Physician Reviewed
Dec 3, 2025
Adrenoleukodystrophy (ALD) is a rare, inherited disorder that damages the brain, spinal cord, and adrenal glands. It primarily affects boys and men, and leads to progressive neurological decline. ALD disrupts the breakdown of very long-chain fatty acids (VLCFAs), which then accumulate and damage the protective sheath (myelin) around nerve cells.
Early diagnosis and intervention are critical for slowing disease progression.
What is Adrenoleukodystrophy?
ALD is a genetic condition linked to the X chromosome that prevents the body from breaking down certain fatty acids. As a result, VLCFAs build up in the brain and adrenal glands, leading to a breakdown of myelin—the protective coating around nerves.
There are multiple forms of ALD, with childhood cerebral ALD being the most severe. Though rare, this condition can be devastating without treatment.
Symptoms
The symptoms of ALD vary depending on the form and age of onset. In the most aggressive form (childhood cerebral ALD), symptoms usually begin between ages 4 and 10.
Early symptoms include:
Behavioral changes (irritability, hyperactivity)
Declining school performance
Difficulty understanding spoken language
Vision or hearing problems
Poor coordination or frequent falls
Darkening of the skin (from adrenal insufficiency)
As the disease progresses:
Seizures
Loss of motor function
Swallowing and speech difficulties
Coma
Death (if untreated within a few years of symptom onset)
Other forms of ALD include:
Adrenomyeloneuropathy (AMN): Gradual stiffness and weakness in legs (usually adult men)
Addison-only ALD: Adrenal failure without neurological symptoms
Causes
ALD is caused by mutations in the ABCD1 gene, which provides instructions for breaking down VLCFAs. The mutation is X-linked, meaning:
Males (with one X chromosome) are more severely affected.
Females (with two X chromosomes) are usually carriers, though some develop mild symptoms
This faulty gene prevents a key protein from transporting VLCFAs into peroxisomes (cellular structures that break down fats), resulting in fatty acid buildup that damages brain cells and the adrenal glands.
Risk Factors
Risk factors are largely genetic. You are at risk if:
You are male with a mutation in the ABCD1 gene
You have a family history of ALD
Your mother is a carrier of the gene mutation
You are a female carrier, which may lead to mild symptoms later in life
Diagnosis
Early detection is critical. ALD may be diagnosed by:
Blood test for VLCFA levels: Elevated levels confirm diagnosis
Genetic testing: Identifies mutations in the ABCD1 gene
MRI scans: Detect early white matter changes in the brain
ACTH stimulation test: Assesses adrenal gland function
Newborn screening: Now performed in many U.S. states to catch ALD early
A diagnosis is often confirmed through genetic sequencing and family history analysis.
Treatments
There is no cure for ALD, but early treatment can slow or halt disease progression in many cases.
For childhood cerebral ALD (early stages):
Hematopoietic stem cell transplant (HSCT): The only treatment shown to stop disease progression—most effective before symptoms appear
Gene therapy (e.g. elivaldogene autotemcel): A promising option under limited approval or clinical trial settings
Lorenzo’s Oil: A mixture of fatty acids that may delay symptom onset in asymptomatic boys, but not effective in advanced stages
Monitoring with MRI every 6–12 months for boys with the gene mutation
For adrenal insufficiency:
Hormone replacement therapy with hydrocortisone or fludrocortisone
For AMN or adult-onset ALD:
Physical therapy
Symptom management (spasticity, urinary issues)
Adrenal hormone therapy if needed
Prevention
ALD itself cannot be prevented, but early intervention can change outcomes.
Here's how:
Newborn screening: Especially critical for families with known ALD history
Carrier testing for women with family history
Early MRI and VLCFA monitoring in asymptomatic boys with confirmed mutation
Pre-pregnancy genetic counseling for families with ALD
Our Take
ALD is one of those diseases where timing can mean the difference between a normal life and rapid neurological decline. That’s why we advocate for newborn screening and family testing—especially for patients of African, Latino, or European descent, where the condition may go unrecognized.
At Covenant, we can coordinate genetic testing, adrenal screening, and partner with transplant centers when needed. The science is moving fast—but so does ALD.
We need to stay ahead of it.
