Cerebral adrenoleukodystrophy (cALD)

Many boys with X-linked ALD in the United States are now found at birth. X-ALD has been on the recommended newborn screening panel since February 2016, and GeneReviews reported in 2023 that more than half of states screened for it. The screen measures a fat called C26:0-lysophosphatidylcholine in the newborn blood spot. A boy with a confirmed ABCD1 gene change is referred to a children's hormone specialist (endocrinologist) to check his adrenal glands. He is also referred to a neurologist or genetics specialist, who plans his brain scans. A girl flagged by the screen does not need monitoring in childhood, but her parents are referred for genetic counseling so male relatives can be checked.

Outside newborn screening, X-ALD is confirmed with a blood test for very long chain fatty acids (VLCFAs) and a genetic test of the ABCD1 gene. International recommendations call the gene test the gold standard. In women, the usual fatty acid test can look nearly normal, so the more sensitive C26:0-lysophosphatidylcholine test is preferred.

The brain form itself is found with brain MRI. Early changes are small and are most often in the corpus callosum, the band that joins the two halves of the brain. Normal scans can sometimes be mistaken for early disease, so experts strongly advise that a neuroradiologist experienced in ALD confirm any finding. Boys who are not being watched are often diagnosed only after symptoms start, and early symptoms are often mistaken for attention or learning problems.

Care starts with close watching, because early brain disease is usually silent. International recommendations advise a first brain MRI at age 2, then scans every 6 months until age 12 and once a year after that. For boys, adrenal blood tests start in the first 6 months of life. In the United States, ALD was added to the recommended newborn screening panel in 2016, but not every state or country screens.

A donor stem cell transplant is the standard treatment for early, active cerebral ALD, and it can stop the brain disease from spreading. Doctors generally consider it for boys when the MRI shows active disease with a Loes score of 9 or less and the boy has no or only mild symptoms. Some adult men with early, active brain disease are also candidates. Results are poor once the disease is advanced, and a transplant does not reliably undo damage that has already happened.

In the United States, a gene therapy called Skysona (elivaldogene autotemcel) adds a working ABCD1 gene to a boy’s own stem cells. Its aim is to slow the loss of brain function. The FDA approved it in 2022 through its accelerated approval pathway for boys 4 to 17 with early, active cerebral ALD. In August 2025, after more blood cancers were found, the FDA limited it to boys without an available HLA-matched donor and strengthened its boxed warning; treated boys need blood tests for life. The European Union approved it in 2021, but the company withdrew it that year for commercial reasons.

When a transplant from a donor is planned, the team usually tests brothers and sisters first. Each full sibling has about a one in four chance of being a full match.

Most patients do not have a matched relative. In the words of NMDP, the U.S. registry, “75% of patients don’t have a fully matched donor in their own family.” The team then searches registries of volunteer donors around the world and banks of donated cord blood. In some transplants, a half-matched parent, child or sibling can also be the donor.

Matching depends on inherited tissue markers called HLA, so a patient is most likely to match someone who shares their ancestry. Every person who joins makes the search a little more likely to succeed, especially for patients from groups that are underrepresented on registries.

Without treatment, cerebral ALD can move fast. GeneReviews says total disability can follow within six months to two years, and death at varying ages after that. In boys who are not treated, brain lesions that light up with contrast dye (gadolinium) on MRI are a strong sign that the disease will keep getting worse.

Timing shapes outlook more than anything else. A transplant has the best results in a boy with no symptoms and only small, early changes on his scan. Results are poorer once the disease is advanced. The main risks include infection, graft failure and, especially in later-stage disease, continued brain decline.

For families living from scan to scan, finding a small, early lesion is frightening. It is also the moment when treatment works best, which is why regular monitoring matters so much.