Metachromatic Leukodystrophy (MLD)
Metachromatic Leukodystrophy (MLD) is a rare genetic condition that affects about 1 in 100,000 babies. It is caused by changes in the ARSA gene, leading to a malfunctioning enzyme and the build-up of fatty substances called sulfatides. The most severe forms develop in early childhood (late-infantile and early-juvenile forms). If detected early, before symptoms appear, a gene therapy (atidarsagene autotemcel) can be administered to improve outcomes. This article reviews the evidence for adding MLD to newborn screening panels in the US. Screening works in two steps using dried blood spots. The first test looks for high levels of sulfatides. If elevated, a second test checks for the activity of the ARSA enzyme. Pilot programs in Germany, Italy and New York City demonstrated the practicality of this two-step approach. In Germany, of the 109,259 newborns screened, 3 (0.8%) cases were detected, and 2 infants received gene therapy. In the US, several states (New York, Illinois, Pennsylvania and Minnesota) are now preparing to add MLD screening to their newborn testing programs. The review concludes that this two-step newborn screening for MLD is accurate with a low rate of false positives. Identifying cases before symptoms begin offers a chance for treatment with gene therapy.