TY  - JOUR
AU  - Adang, Laura A
AU  - Bonkowsky, Joshua L
AU  - Boelens, Jaap Jan
AU  - Mallack, Eric
AU  - Ahrens-Nicklas, Rebecca
AU  - Bernat, John A
AU  - Bley, Annette
AU  - Burton, Barbara
AU  - Darling, Alejandra
AU  - Eichler, Florian
AU  - Eklund, Erik
AU  - Emrick, Lisa
AU  - Escolar, Maria
AU  - Fatemi, Ali
AU  - Fraser, Jamie L
AU  - Gaviglio, Amy
AU  - Keller, Stephanie
AU  - Patterson, Marc C
AU  - Orchard, Paul
AU  - Orthmann-Murphy, Jennifer
AU  - Santoro, Jonathan D
AU  - Schöls, Ludger
AU  - Sevin, Caroline
AU  - Srivastava, Isha N
AU  - Rajan, Deepa
AU  - Rubin, Jennifer P
AU  - Van Haren, Keith
AU  - Wasserstein, Melissa
AU  - Zerem, Ayelet
AU  - Fumagalli, Francesca
AU  - Laugwitz, Lucia
AU  - Vanderver, Adeline
TI  - Consensus guidelines for the monitoring and management of metachromatic leukodystrophy in the United States.
JO  - Cytotherapy
VL  - 26
IS  - 7
SN  - 1465-3249
CY  - Abingdon
PB  - Taylor & Francis Group
M1  - DZNE-2024-00853
SP  - 739 - 748
PY  - 2024
AB  - 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.
KW  - Humans
KW  - Infant, Newborn
KW  - Cerebroside-Sulfatase: genetics
KW  - Consensus
KW  - Genetic Therapy: methods
KW  - Leukodystrophy, Metachromatic: therapy
KW  - Leukodystrophy, Metachromatic: diagnosis
KW  - Leukodystrophy, Metachromatic: genetics
KW  - Neonatal Screening: methods
KW  - United States
KW  - gene therapy (Other)
KW  - leukodystrophy (Other)
KW  - metachromatic leukodystrophy (Other)
KW  - newborn screening (Other)
KW  - transplant (Other)
KW  - Cerebroside-Sulfatase (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C2  - pmc:PMC11348704
C6  - pmid:38613540
DO  - DOI:10.1016/j.jcyt.2024.03.487
UR  - https://pub.dzne.de/record/270681
ER  -