ArticleOrphanet journal of rare diseases2019
Phenotypic variation between siblings with Metachromatic Leukodystrophy.
Article in Orphanet journal of rare diseases, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers, 2 of them syntheses that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
24 citing papers in PubMed, 2 syntheses or guidelines pooled it, 50 citations in OpenAlex.
- Consensus guidelines for the monitoring and management of metachromatic leukodystrophy in the United States.Cytotherapy · 2024Guideline
- The natural history and burden of illness of metachromatic leukodystrophy: a systematic literature review.European journal of medical research · 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
- ARSA Variants Associated With Cognitive Decline and Long-Term Preservation of Motor Function in Metachromatic Leukodystrophy.Journal of inherited metabolic disease · 2025Observational
- Metachromatic Leukodystrophy: New Therapy Advancements and Emerging Research Directions.Neurology · 2025Review
- Characterizing Diagnostic Delays in Metachromatic Leukodystrophy: A Real-World Data Approach.Journal of inherited metabolic disease · 2025Article
- Characterization of gallbladder disease in metachromatic leukodystrophy across the lifespan.Molecular genetics and metabolism · 2025Article
- Developmental delay can precede neurologic regression in early onset metachromatic leukodystrophy.Molecular genetics and metabolism · 2024Article
- Systematic analysis of genotype-phenotype variability in siblings with Aicardi Goutières Syndrome (AGS).Molecular genetics and metabolism · 2024Article
- MALDI-TOF MS combined with AUC method for tigecycline susceptibility testing inJAC-antimicrobial resistance · 2024Article
- Atidarsagene autotemcel for metachromatic leukodystrophy.Journal of managed care & specialty pharmacy · 2024Article
- A retrospective cohort study of Libmeldy (atidarsagene autotemcel) for MLD: What we have accomplished and what opportunities lie ahead.JIMD reports · 2023Article
- Predicting disease severity in metachromatic leukodystrophy using protein activity and a patient phenotype matrix.Genome biology · 2023Article
- Rapidly progressive dementias - leukodystrophies as a potentially treatable cause.Nature reviews. Neurology · 2022Article
- Recognizing early MRI signs (or their absence) is crucial in diagnosing metachromatic leukodystrophy.Annals of clinical and translational neurology · 2022Article
- An international study of caregiver-reported burden and quality of life in metachromatic leukodystrophy.Orphanet journal of rare diseases · 2022Article
- Neurofilament light chain and glial fibrillary acidic protein levels in metachromatic leukodystrophy.Brain : a journal of neurology · 2022Article
- Modified Delphi procedure-based expert consensus on endpoints for an international disease registry for Metachromatic Leukodystrophy: The European Metachromatic Leukodystrophy initiative (MLDi).Orphanet journal of rare diseases · 2022Article
- Rare Diseases in Glycosphingolipid Metabolism.Advances in experimental medicine and biology · 2022Article
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundMetachromatic Leukodystrophy (MLD) is a rare autosomal-recessive lysosomal storage disorder caused by mutations in the ARSA gene. While interventional trials often use untreated siblings as controls, the genotype-phenotype correlation is only partly understood, and the variability of the clinical course between siblings is unclear with some evidence for a discrepant clinical course in juvenile patients. The aim of this study was to systematically investigate the phenotypic variation in MLD siblings in comparison to the variability in a larger MLD cohort and to case reports published in literature.
resultsDetailed clinical information was available from 12 sibling-pairs (3 late-infantile, 9 juvenile) and 61 single patients (29 late-infantile, 32 juvenile). Variability of age at onset was similar between the siblings and randomly chosen pairs of the remaining cohort (no statistically different Euclidean distances). However, in children with juvenile MLD both the type of first symptoms and the dynamic of the disease were less variable between siblings compared to the general cohort. In late-infantile patients, type of first symptoms and dynamic of disease were similarly homogeneous between siblings and the whole MLD cohort. Thirteen published case reports of families with affected siblings with MLD are presented with similar findings.
conclusionsIn a systematic analysis of phenotypic variation in families with MLD, siblings with the late-infantile form showed a similar variability as unrelated pairs of children with late-infantile MLD, whereas siblings with juvenile MLD showed a more homogeneous phenotype regarding type of first symptoms and disease evolution in comparison to unrelated children with juvenile MLD, but not regarding their age at onset. These results are highly relevant with respect to the evaluation of treatment effects and for counseling of families with affected siblings.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.