Late-juvenile metachromatic leukodystrophy (MLD)

Late-juvenile MLD is usually suspected when a child or teen who was developing normally starts to slip in school, behavior or movement. The care team then orders a brain MRI. It usually shows damage to the white matter, the parts of the brain made mostly of myelin. Nerve conduction studies, which measure how well signals travel along the nerves in the arms and legs, are often done too, to see how far the nerve damage has gone and to track it over time.

U.S. expert guidance says the diagnosis should rest on both lab chemistry and genetics. The tests look for low activity of the enzyme arylsulfatase A in white blood cells, high levels of fatty substances called sulfatides in the urine, and two disease-causing changes in the ARSA gene. Together with family history, these results help doctors predict which form of MLD a person has, and that shapes the treatment options.

Early signs start slowly and can go unrecognized for months or years. Some young people are found before any symptoms because a brother or sister was diagnosed first. A few are found after gallbladder problems. In December 2025, MLD was added to the U.S. Recommended Uniform Screening Panel, the national list of conditions recommended for newborn screening. Each state decides what it screens for, so whether a baby is screened depends on where they are born.

The main treatment that can change the course of late-juvenile MLD is an allogeneic stem cell transplant. After conditioning chemotherapy, the person receives blood-forming cells from a donor. Some donor cells slowly settle in the brain, and over time this can help slow the damage. Experts are still learning exactly how it works.

US expert guidance says a transplant should be considered for people with late-onset MLD who have no symptoms or only minimal ones. European transplant recommendations list MLD as a standard reason for transplant in suitable patients. Benefit is greatest before symptoms begin. A transplant does not fully protect the nerves in the arms and legs, and when it is done after walking problems start, it can even speed up decline in some people.

Transplant carries serious risks, including infection, graft-versus-host disease, graft failure and death. A 2025 international review said that about 10 to 15 in 100 people with MLD who have a transplant die from its complications, and more in some groups. The gene therapy approved for early-onset MLD is being tested for this form in a clinical trial in Italy. As of September 2026, that trial was no longer taking new patients, and the therapy was not approved for this form. Therapy, school support, seizure treatment and gallbladder checks remain part of care.

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.

Late-juvenile MLD usually moves more slowly than the forms that begin in early childhood, and its course can stretch over years or even decades. Without treatment, it keeps getting worse. Across all juvenile forms, most people die before age 20, although survival varies widely. Movement problems at the start of the illness point to a faster course. Once movement skills begin to decline, the loss of skills tends to be fast.

For transplant, a key factor is how much movement and thinking a person still has when treatment is considered. A donor transplant can steady the brain disease in some people, and it helps most before symptoms or while they are still minimal. One research group found that people who could no longer walk without support, or whose IQ had fallen below 75, did not benefit. In one large U.S. group, nerve tests in the arms and legs often kept getting worse after transplant, even when brain scans stayed stable.

These are hard facts to read about a young person who may still seem mostly well. Every course is different, and the numbers below describe groups of people, not one child or teen.