Metachromatic Leukodystrophy (MLD)
https://publications.aap.org/pediatrics/article/158/Supplement%202/e2026077357E/208745
Metachromatic leukodystrophy (MLD) is a rare, inherited metabolic disorder affecting approximately one in 100,000 newborns. It results from changes in both copies of the ARSA gene, which reduce the activity of an enzyme needed to break down fatty substances called sulfatides. These substances accumulate in the nervous system, damaging myelin, the protective coating around nerve fibres. This process, known as demyelination, can cause progressive neurological deterioration, including difficulties with movement, swallowing and vision. This article reviews the evidence supporting newborn screening for MLD, focusing on early-onset forms that can progress rapidly during childhood. Without screening, diagnosis often occurs after symptoms develop, when significant and potentially irreversible damage may already have occurred. Importantly, gene therapy delivered during infancy can improve survival and motor function, making early diagnosis particularly valuable. The proposed screening approach uses a two-step process. First, a dried blood spot collected from a newborn is tested for elevated sulfatides. If levels are raised, a second test measures arylsulfatase A (ARSA) enzyme activity. Research suggests this approach can identify early-onset MLD accurately, with a low rate of false-positive results. However, screening is not designed to identify every form of MLD, particularly later-onset types. Pilot screening programmes are underway in the United States, while population-based programmes operate in parts of Europe. New York and Pennsylvania in the US and Norway have MLD on their NBS programs as do parts of Germany. Hannover, Germany, has reported identifying affected infants through newborn screening, enabling timely access to treatment. Overall, the evidence supports the potential benefits of introducing MLD newborn screening. Earlier detection could provide families with timely diagnoses and access to treatment before symptoms emerge. Further implementation and evaluation will help establish how screening can best improve outcomes for children affected by this devastating condition.