Consensus guidelines for the monitoring and management of metachromatic leukodystrophy in the United States
(2024) In Cytotherapy 26(7). p.739-748- Abstract
Metachromatic leukodystrophy (MLD) is a fatal, progressive neurodegenerative disorder caused by biallelic pathogenic mutations in the ARSA (Arylsulfatase A) gene. With the advent of presymptomatic diagnosis and the availability of therapies with a narrow window for intervention, it is critical to define a standardized approach to diagnosis, presymptomatic monitoring, and clinical care. To meet the needs of the MLD community, a panel of MLD experts was established to develop disease-specific guidelines based on healthcare resources in the United States. This group developed a consensus opinion for best-practice recommendations, as follows: (i) Diagnosis should include both genetic and biochemical testing; (ii) Early diagnosis and... (More)
Metachromatic leukodystrophy (MLD) is a fatal, progressive neurodegenerative disorder caused by biallelic pathogenic mutations in the ARSA (Arylsulfatase A) gene. With the advent of presymptomatic diagnosis and the availability of therapies with a narrow window for intervention, it is critical to define a standardized approach to diagnosis, presymptomatic monitoring, and clinical care. To meet the needs of the MLD community, a panel of MLD experts was established to develop disease-specific guidelines based on healthcare resources in the United States. This group developed a consensus opinion for best-practice recommendations, as follows: (i) Diagnosis should include both genetic and biochemical testing; (ii) Early diagnosis and treatment for MLD is associated with improved clinical outcomes; (iii) The panel supported the development of newborn screening to accelerate the time to diagnosis and treatment; (iv) Clinical management of MLD should include specialists familiar with the disease who are able to follow patients longitudinally; (v) In early onset MLD, including late infantile and early juvenile subtypes, ex vivo gene therapy should be considered for presymptomatic patients where available; (vi) In late-onset MLD, including late juvenile and adult subtypes, hematopoietic cell transplant (HCT) should be considered for patients with no or minimal disease involvement. This document summarizes current guidance on the presymptomatic monitoring of children affected by MLD as well as the clinical management of symptomatic patients. Future data-driven evidence and evolution of these recommendations will be important to stratify clinical treatment options and improve clinical care.
(Less)
- author
- organization
- publishing date
- 2024-07
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- gene therapy, leukodystrophy, metachromatic leukodystrophy, newborn screening, transplant
- in
- Cytotherapy
- volume
- 26
- issue
- 7
- pages
- 10 pages
- publisher
- Taylor & Francis
- external identifiers
-
- scopus:85190294942
- pmid:38613540
- ISSN
- 1465-3249
- DOI
- 10.1016/j.jcyt.2024.03.487
- language
- English
- LU publication?
- yes
- id
- f84e2183-0f44-443f-960b-666d41998c4a
- date added to LUP
- 2025-01-08 11:28:38
- date last changed
- 2025-07-10 16:02:13
@article{f84e2183-0f44-443f-960b-666d41998c4a,
abstract = {{<p>Metachromatic leukodystrophy (MLD) is a fatal, progressive neurodegenerative disorder caused by biallelic pathogenic mutations in the ARSA (Arylsulfatase A) gene. With the advent of presymptomatic diagnosis and the availability of therapies with a narrow window for intervention, it is critical to define a standardized approach to diagnosis, presymptomatic monitoring, and clinical care. To meet the needs of the MLD community, a panel of MLD experts was established to develop disease-specific guidelines based on healthcare resources in the United States. This group developed a consensus opinion for best-practice recommendations, as follows: (i) Diagnosis should include both genetic and biochemical testing; (ii) Early diagnosis and treatment for MLD is associated with improved clinical outcomes; (iii) The panel supported the development of newborn screening to accelerate the time to diagnosis and treatment; (iv) Clinical management of MLD should include specialists familiar with the disease who are able to follow patients longitudinally; (v) In early onset MLD, including late infantile and early juvenile subtypes, ex vivo gene therapy should be considered for presymptomatic patients where available; (vi) In late-onset MLD, including late juvenile and adult subtypes, hematopoietic cell transplant (HCT) should be considered for patients with no or minimal disease involvement. This document summarizes current guidance on the presymptomatic monitoring of children affected by MLD as well as the clinical management of symptomatic patients. Future data-driven evidence and evolution of these recommendations will be important to stratify clinical treatment options and improve clinical care.</p>}},
author = {{Adang, Laura A. and Bonkowsky, Joshua L. and Boelens, Jaap Jan and Mallack, Eric and Ahrens-Nicklas, Rebecca and Bernat, John A. and Bley, Annette and Burton, Barbara and Darling, Alejandra and Eichler, Florian and Eklund, Erik and Emrick, Lisa and Escolar, Maria and Fatemi, Ali and Fraser, Jamie L. and Gaviglio, Amy and Keller, Stephanie and Patterson, Marc C. and Orchard, Paul and Orthmann-Murphy, Jennifer and Santoro, Jonathan D. and Schöls, Ludger and Sevin, Caroline and Srivastava, Isha N. and Rajan, Deepa and Rubin, Jennifer P. and Van Haren, Keith and Wasserstein, Melissa and Zerem, Ayelet and Fumagalli, Francesca and Laugwitz, Lucia and Vanderver, Adeline}},
issn = {{1465-3249}},
keywords = {{gene therapy; leukodystrophy; metachromatic leukodystrophy; newborn screening; transplant}},
language = {{eng}},
number = {{7}},
pages = {{739--748}},
publisher = {{Taylor & Francis}},
series = {{Cytotherapy}},
title = {{Consensus guidelines for the monitoring and management of metachromatic leukodystrophy in the United States}},
url = {{http://dx.doi.org/10.1016/j.jcyt.2024.03.487}},
doi = {{10.1016/j.jcyt.2024.03.487}},
volume = {{26}},
year = {{2024}},
}