Leukodystrophies

Leukodystrophies are a group of rare genetic disorders of the central nervous system, which is the brain and spinal cord. They damage its white matter: the nerve fibers that connect nerve cells, and myelin, the layer of proteins and fats that covers and protects those fibers. MedlinePlus says there are more than 50 types. Some are present at birth, while others may not cause symptoms until a child becomes a toddler. A few types mainly affect adults.

For some types, yes, if it is done early. NMDP lists cerebral X-linked adrenoleukodystrophy, Krabbe disease and metachromatic leukodystrophy among the inherited metabolic disorders a donor transplant can treat. NMDP explains that a transplant brings in healthy cells that make the missing enzyme and can cross into the brain. International ALD experts call a transplant the treatment of choice for cerebral ALD. European transplant guidance says it does not work in the earliest-onset MLD, and it is not recommended once cerebral ALD is advanced. MedlinePlus notes that there is no cure for leukodystrophies, and that a stem cell or bone marrow transplant can help with a few types.

Yes, for two of them. For MLD, a gene therapy made from the child’s own stem cells, called Lenmeldy in the U.S., was FDA-approved on March 18, 2024. It is for children with late-infantile or early-juvenile MLD before symptoms, and early-juvenile MLD with early symptoms. In the European Union it has been approved as Libmeldy since December 17, 2020. For cerebral ALD, Skysona was approved in the U.S. in 2022 for boys aged 4 to 17 with early, active disease. After blood cancers were found in 10 of 67 clinical trial participants, the FDA limited it in August 2025 to boys without an available HLA-matched donor. It is not available in the European Union. For infantile Krabbe disease, U.S. experts wrote in 2026 that a donor transplant is the only treatment available that can change the course of the disease.

Transplant and gene therapy work best before symptoms, or very early. For infantile Krabbe disease, U.S. consensus guidelines ask for referral to a transplant center no later than the third week of life, so transplant can start within the first 4 weeks. For cerebral ALD, international experts say the outcome is poor once the disease is advanced. That means a Loes score above 9 or a neurologic function score above 1. For MLD, U.S. experts advise considering gene therapy for early-onset forms before symptoms, where it is available. For later-onset forms, they advise considering a donor transplant when there are no or few signs of disease.

In the U.S., three of them are on the federal Recommended Uniform Screening Panel. X-linked ALD was added in February 2016 and infantile Krabbe disease on July 1, 2024. MLD followed in a notice published December 22, 2025. States choose their own methods, and not every state screens for every condition yet. As of November 2025, 16 more states had adopted Krabbe screening. For ALD, a 2022 study reported that fewer than half of U.S. states, and no European countries, screened at that time.

MLD and Krabbe disease are autosomal recessive. A child is affected when both copies of the gene carry a change: ARSA (or, rarely, PSAP) in MLD, and GALC in Krabbe disease. The parents each carry one changed copy but usually have no signs. X-linked ALD comes from a change in the ABCD1 gene on the X chromosome. In males, one changed copy is enough to cause it. A man with ALD passes the changed gene to all of his daughters and none of his sons. A woman with one changed copy has a 50 percent chance of passing it to each of her children.