Juvenile metachromatic leukodystrophy caused by a rare genetic mutation.

Metachromatic leukodystrophy (MLD) is a lysosomal storage disease caused by a deficiency of arylsulfatase A (ASA), with several clinical variants. A clinical report of juvenile MLD caused by a rare genetic mutation was characterized over time. This study aims to describe the disease progression through the analysis of long-term data. This is a retrospective observational study in which clinical, genetic, and biochemical parameters were analyzed. Changes in neuroanatomical patterns were analyzed by MRI over time. N-acetylaspartate (NAA) variation was also measured. This study is one of the first to report a rare splice-site mutation (c.1211–2 A > G) in the ARSA gene associated with juvenile MLD. MRI analysis revealed frontal periventricular hyperintensity, demyelination of the corpus callosum and development of a tigroid pattern. The cerebellum was less affected over time. Reduction in NAA levels was consistent with clinical symptoms. This study enhances understanding of the disease progression in juvenile MLD, contributing to the differentiation of MLD subtypes and supporting improved clinical management and counseling for patients with MLD.