Metachromatic leukodystrophy: To screen or not to screen?

• Published in: European journal of paediatric neurology Vol. 46; pp. 1 - 7
• Main Authors: Jonckheere, An I., Kingma, Sandra D.K., Eyskens, François, Bordon, Victoria, Jansen, Anna C.
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.09.2023
• Subjects: Metachromatic leukodystrophy; Newborn screening; Treatment; Newborn screening; Metachromatic leukodystrophy; Treatment
• ISSN: 1090-3798; 1532-2130
• DOI: 10.1016/j.ejpn.2023.06.005

Metachromatic leukodystrophy (MLD) is a neurodegenerative lysosomal storage disorder caused by biallelic pathogenic variants in the gene encoding arylsulfatase A. Disease onset is variable (with late infantile, early and late juvenile, and adult forms) and treatment options depend on age and disease symptoms at onset. In the past, allo-hematopoietic stem cell transplantation (allo-HSCT) has been the best treatment option, following strict selection criteria. The outcome however is variable and morbidity remains high. This paved the way to the development of new treatment options, some of them aiming to be curative. In the light of this changing therapeutic field, newborn screening is becoming a valuable option. This narrative review aims to describe the outcome of allo-HSCT in the different MLD disease forms, and, in addition, reviews new treatment options. Finally, the shift of the field towards newborn screening for MLD is discussed. •MLD is a neurodegenerative disease.•Allo-hematopoietic stem cell transplantation increases life span but morbidity remains high.•New therapeutic developments including gene therapy aim to be curative.•This shifts the field towards newborn screening.