{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:17:11Z","timestamp":1788221831858,"version":"build-2803163510"},"reference-count":18,"publisher":"American Academy of Pediatrics (AAP)","issue":"Supplement 2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,9,1]]},"abstract":"<jats:p>Metachromatic leukodystrophy (MLD) is a lysosomal disorder affecting approximately 1 per 100\u2009000 newborns. It is caused by biallelic variations in the arylsulfatase A (ARSA) gene, leading to deficiency of ARSA enzyme activity and elevation of sulfatides. Most affected individuals have the late-infantile or early-juvenile phenotype, associated with significant and progressive neurologic degeneration and death. For these phenotypes, treatment with a lentiviral gene therapy in infancy can improve survival and motor function. However, in the absence of screening or an affected older sibling, most cases are diagnosed much later. A 2-tiered newborn screen, based on the presence of elevated sulfatides in dried blood spots followed by finding low ARSA enzyme activity, can accurately identify newborns with the early-onset phenotypes of MLD for timely gene therapy. An MLD screening study with consent is ongoing in 8 hospitals in New York City, and population-based newborn screening has been implemented in several regions in Europe. Although the false-positive rate is low, only 1 of these MLD newborn screening activities, in Hannover, Germany, has reported identifying cases. At least 4 newborn screening programs in the United States are in the process of implementing MLD screening.<\/jats:p>","DOI":"10.1542\/peds.2026-077357e","type":"journal-article","created":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:02:56Z","timestamp":1788220976000},"source":"Crossref","is-referenced-by-count":0,"title":["Evidence Regarding Metachromatic Leukodystrophy Newborn Screening"],"prefix":"10.1542","volume":"158","author":[{"given":"Wendy K.K.","family":"Lam","sequence":"first","affiliation":[{"name":"1Duke Clinical and Translational Science Institute, Duke University School of Medicine, Durham, North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margie A.","family":"Ream","sequence":"additional","affiliation":[{"name":"2Division of Child Neurology, Nationwide Children\u2019s Hospital, Columbus, Ohio"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott 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