Language

English

Publication Date

7-1-2024

Journal

Cytotherapy

DOI

10.1016/j.jcyt.2024.03.487

PMID

38613540

PMCID

PMC11348704

PubMedCentral® Posted Date

7-1-2025

PubMedCentral® Full Text Version

Author MSS

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 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.

Keywords

Humans, Infant, Newborn, Cerebroside-Sulfatase, Consensus, Genetic Therapy, Leukodystrophy, Metachromatic, Neonatal Screening, United States, newborn screening, transplant, gene therapy, leukodystrophy, metachromatic leukodystrophy

Published Open-Access

yes

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