Late-infantile metachromatic leukodystrophy (MLD)

Most children are diagnosed after symptoms start. A child neurologist (brain and nerve doctor) or a genetics doctor usually leads the testing. A brain MRI shows damage to the white matter, the parts of the brain made of nerve fibers wrapped in myelin. Blood and urine tests check the arylsulfatase A enzyme, look for high sulfatides in the urine, and search for changes in both copies of the ARSA gene.

The road to a diagnosis is often long. In one U.S. study of 16 children with late-infantile MLD, first signs appeared at about 1½ years old on average, but diagnosis came at about 2½. Early signs were sometimes first called developmental delay. Some children are found before symptoms because an older brother or sister was diagnosed.

Newborn screening is starting to change this. On September 12, 2025, New York became the first U.S. state to screen all newborns for MLD, as a pilot. The test measures sulfatides in the newborn blood spot, and enzyme and genetic tests confirm a positive result. Illinois, Minnesota and Pennsylvania have approved adding MLD, and the federal government added it to the recommended list in December 2025. Norway has screened all newborns since January 2025, and large pilots are running in Germany, Austria and Italy.

The only approved treatment that changes the course of late-infantile MLD is a gene therapy called atidarsagene autotemcel. It is sold as Libmeldy in the European Union (approved December 2020) and the UK, and as Lenmeldy in the United States (approved March 2024). For this form, it is approved only for children who do not have symptoms yet.

Doctors collect the child’s own blood-forming stem cells, and a lab adds a working copy of the ARSA gene. The child then gets strong chemotherapy (conditioning), and the corrected cells are given back through an IV.

The treatment carries real risks, including serious infections. In the studies, one child died of a stroke caused by a blood clot, and another had brain inflammation (encephalitis). There is also a possible risk of blood cancer, so children need yearly blood checks, though no cases had been reported when the US label was written. Half of the girls in the studies later had ovarian failure, meaning their ovaries stopped working.

For children who already have symptoms, care focuses on comfort and daily life. This can include physical therapy, feeding help or a feeding tube, medicines for seizures, pain and stiff muscles, and breathing support. Other approaches, such as enzyme given into the spinal fluid or gene therapy injected into the brain, did not show a clear benefit in trials.

Without treatment, late-infantile MLD takes away movement, speech and awareness over several years. How long children live varies, and many live for several years after symptoms begin. This is one of the hardest diagnoses a family can face. Comfort care and family support matter from the start.

Children found before symptoms and treated with gene therapy have done much better in studies. Most kept the ability to walk on their own for years, and all 14 treated children followed to age 6 were alive. Results were not perfect: a few children still lost the ability to walk, and two never walked on their own. For this form, gene therapy is not approved once symptoms have started, and it cannot undo damage that has already happened.