ArticleGenetics in medicine : official journal of the American College of Medical Genetics2021
Toward newborn screening of metachromatic leukodystrophy: results from analysis of over 27,000 newborn dried blood spots.
Article in Genetics in medicine : official journal of the American College of Medical Genetics, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers, 2 of them syntheses that pooled it.
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Who cites it
43 citing papers in PubMed, 2 syntheses or guidelines pooled it.
- Consensus guidelines for the monitoring and management of metachromatic leukodystrophy in the United States.Cytotherapy · 2024Guideline
- A systematic review on the birth prevalence of metachromatic leukodystrophy.Orphanet journal of rare diseases · 2024Pooled it
- Lentiviral haematopoietic stem-cell gene therapy for early-onset metachromatic leukodystrophy: long-term results from a non-randomised, open-label, phase 1/2 trial and expanded access.Lancet (London, England) · 2022Trial
- Clinical management of metachromatic leukodystrophy cases identified in the German and Austrian Newborn screening pilots.Orphanet journal of rare diseases · 2026Article
- Multi-modal recruitment efficiency in ScreenPlus, a large-scale consented pilot NBS program.medRxiv : the preprint server for health sciences · 2026Article
- Preliminary Data of the First Year of Newborn Screening for Metachromatic Leukodystrophy (MLD) in Lombardy.International journal of neonatal screening · 2026Article
- Insights from the LysoNeo prospective cohort study to improve newborn screening of lysosomal diseases.Communications medicine · 2026Article
- Developing a National Network for Leukodystrophy Research and Care in Canada: The CARELeuko Initiative.Neurology. Genetics · 2025Review
- Newborn Screening for Metachromatic Leukodystrophy: A Systematic Literature Review.International journal of neonatal screening · 2025Review
- Metachromatic Leukodystrophy: New Therapy Advancements and Emerging Research Directions.Neurology · 2025Review
- Screening for Life: Perspectives From Adult Metabolic Specialists on Newborn Screening for Inherited Metabolic Diseases.Journal of inherited metabolic disease · 2025Review
- Characterizing Diagnostic Delays in Metachromatic Leukodystrophy: A Real-World Data Approach.Journal of inherited metabolic disease · 2025Article
- Newborn screening for metachromatic leukodystrophy: Preparation of reagents and methodology for measurement of sulfatides and arylsulfatase A enzymatic activity in dried blood spots.Molecular genetics and metabolism · 2025Article
- Healthcare utilization and disease burden in children with metachromatic leukodystrophy in Germany.Orphanet journal of rare diseases · 2025Article
- Newborn Screening for Metachromatic Leukodystrophy in Tuscany: The Paradigm of a Successful Preventive Medicine Program.International journal of neonatal screening · 2025Article
- Newborn screening and rapid genomic diagnosis of neuromuscular diseases.Journal of neuromuscular diseases · 2025Review
- Evaluation of enzyme activity predictions for variants of unknown significance in Arylsulfatase A.Human genetics · 2025Article
- Does Early Diagnosis and Treatment Alter the Clinical Course of Wolman Disease? Divergent Trajectories in Two Siblings and a Consideration for Newborn Screening.International journal of neonatal screening · 2025Article
- Article
- Hematopoietic stem cell gene therapy improves outcomes in a clinically relevant mouse model of multiple sulfatase deficiency.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
Corrections and comments
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Authors and funding
12 authors.
Funding
Abstract
purposeMetachromatic leukodystrophy (MLD) is a lysosomal storage disorder caused by the deficiency of arylsulfatase A (ARSA), which results in the accumulation of sulfatides. Newborn screening for MLD may be considered in the future as innovative treatments are advancing. We carried out a research study to assess the feasibility of screening MLD using dried blood spots (DBS) from de-identified newborns.
methodsTo minimize the false-positive rate, a two-tier screening algorithm was designed. The primary test was to quantify C16:0-sulfatide in DBS by ultraperformance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). The screening cutoff was established based on the results from 15 MLD newborns to achieve 100% sensitivity. The secondary test was to measure the ARSA activity in DBS from newborns with abnormal C16:0-sulfatide levels. Only newborns that displayed both abnormal C16:0-sulfatide abundance and ARSA activity were considered screen positives.
resultsA total of 27,335 newborns were screened using this two-tier algorithm, and 2 high-risk cases were identified. ARSA gene sequencing identified these two high-risk subjects to be a MLD-affected patient and a heterozygote.
conclusionOur study demonstrates that newborn screening for MLD is highly feasible in a real-world scenario with near 100% assay specificity.
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