ArticleMolecular genetics and metabolism2024
Developmental delay can precede neurologic regression in early onset metachromatic leukodystrophy.
Article in Molecular genetics and metabolism, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers, 1 of them a synthesis that pooled it.
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Who cites it
8 citing papers in PubMed, 1 synthesis or guideline pooled it.
- The natural history and burden of illness of metachromatic leukodystrophy: a systematic literature review.European journal of medical research · 2024Pooled it
- Developmental trajectory of individuals with Pelizaeus-Merzbacher Disease (PMD).Molecular genetics and metabolism · 2026Article
- Rigorous genetic diagnosis review in natural history studies.Orphanet journal of rare diseases · 2026Article
- Article
- Exploration Into Lived Experiences of Multiple Sulfatase Deficiency-Affected Individuals and Their Families.Journal of child neurology · 2025Article
- Metachromatic Leukodystrophy: New Therapy Advancements and Emerging Research Directions.Neurology · 2025Review
- Molecular Insights into Neurological Regression with a Focus on Rett Syndrome-A Narrative Review.International journal of molecular sciences · 2025Review
- Lenmeldy (atidarsagene autotemcel) for individuals with early metachromatic leukodystrophy (MLD): A therapeutics bulletin of the American College of Medical Genetics and Genomics (ACMG).Genetics in medicine open · 2025Article
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Authors and funding
48 authors.
Funding
Abstract
objectiveMetachromatic leukodystrophy (MLD) is a rare neurodegenerative disorder. Emerging therapies are most effective in the presymptomatic phase, and thus defining this window is critical. We hypothesize that early development delay may precede developmental plateau. With the advent of presymptomatic screening platforms and transformative therapies, it is essential to define the onset of neurologic disease.
methodsThe specific ages of gain and loss of developmental milestones were captured from the medical records of individuals affected by MLD. Milestone acquisition was characterized as: on target (obtained before the age limit of 90th percentile plus 2 standard deviations compared to a normative dataset), delayed (obtained after 90th percentile plus 2 standard deviations), or plateau (skills never gained). Regression was defined as the age at which skills were lost. LI-MLD was defined by age at onset before 2.5 years.
resultsAcross an international cohort, 351 subjects were included (n = 194 LI-MLD subcohort). The median age at presentation of the LI-MLD cohort was 1.4 years (25th-75th %ile: 1.0-1.5). Within the LI-MLD cohort, 75/194 (39%) had developmental delay (or plateau) prior to MLD clinical presentation. Among the LI-MLD cohort with a minimum of 1.5 years of follow-up (n = 187), 73 (39.0%) subjects never attained independent ambulation. Within LI-MLD + delay subcohort, the median time between first missed milestone target to MLD decline was 0.60 years (maximum distance from delay to onset: 1.9 years).
interpretationEarly developmental delay precedes regression in a subset of children affected by LI-MLD, defining the onset of neurologic dysfunction earlier than previously appreciated. The use of realworld data prior to diagnosis revealed an early deviation from typical development. Close monitoring for early developmental delay in presymptomatic individuals may help in earlier diagnosis with important consequences for treatment decisions.
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