Adult-onset metachromatic leukodystrophy (MLD)

Adult MLD is often first suspected when a brain MRI shows damage to the white matter, the parts of the brain made of nerve fibers wrapped in myelin. In later-onset MLD, these MRI changes show up before symptoms do. Early signs are often changes in mood, behavior or thinking, so the first specialist may be a psychiatrist or another mental health provider. A nerve test (nerve conduction study) is often done too, to look for damage to the nerves of the arms and legs.

Three kinds of tests confirm it. A blood test measures the enzyme arylsulfatase A in white blood cells. A urine test measures sulfatides, the fatty substances that build up. A genetic test looks for changes in both copies of the ARSA gene. U.S. expert guidance says diagnosis should include both the genetic test and the enzyme and sulfatide tests. One reason is pseudodeficiency. About 1 to 2 in 100 people of European descent have a low enzyme result from harmless gene changes, without having MLD.

When symptoms are mainly about thinking or mood, it can take years to reach the right diagnosis. In December 2025, MLD was added to the U.S. list of conditions recommended for newborn screening. Each state decides whether and when to screen for it. New York began screening all newborns in September 2025, as a one-year pilot. Screening can also find babies who will get MLD later in life. A German pilot of 109,259 newborns found three babies with MLD, and one had a later-onset form.

No approved medicine treats the cause of adult-onset MLD. Care focuses on symptoms and daily life. It can include psychiatric care, seizure medicines, physical and occupational therapy, help with speech, swallowing and nutrition, and planning for changing needs.

An allogeneic stem cell transplant, using a donor’s blood-forming cells, may be considered for adults found before symptoms or with only minimal ones. US expert guidance supports considering it in that group. European transplant recommendations use the same reasons for transplant in adults as in children and advise getting guidance from a specialist center. The evidence in adults is small, and results depend strongly on how early treatment happens.

In a European registry of people with late-juvenile and adult-onset MLD, those transplanted before symptoms did best, but a transplant could not always stop decline. The gene therapy approved for early-onset MLD in children does not cover adults, and a 2025 review said it was not yet being studied in adult-onset MLD.

Adult MLD usually moves slowly. People with the adult form may live 20 to 30 years after diagnosis, with times of stability and times of faster decline. A 2025 review described life expectancy in the adult form as ranging from several years to decades.

Two things shape the outlook most: the kind of first symptoms, and how early treatment happens. People whose illness begins with thinking or behavior changes alone tend to decline more slowly than people who start with movement problems. Once movement starts to get worse, decline tends to speed up, whatever the age at onset.

A donor stem cell transplant helps most when it is done before symptoms start. In the largest European group studied so far, people transplanted before symptoms were the least likely to reach an advanced stage. Even so, a transplant could not always stop the disease, and most people with MLD are diagnosed too late to benefit. At every stage, care for mood, movement, eating and comfort remains part of treatment.