Abstract
Sialidosis is a rare autosomal recessive lysosomal storage disorder caused by mutations in the NEU1 gene, resulting in deficient neuraminidase-1 activity and the subsequent accumulation of sialylated compounds in lysosomes. This review comprehensively analyzes the genetic and clinical heterogeneity associated with sialidosis, emphasizing the distinction between the milder type I form and the more severe type II form. Over 90 pathogenic NEU1 variants, predominantly missense mutations, have been identified, highlighting significant phenotypic diversity. Advancements in genomic sequencing technologies have facilitated the identification of known and novel mutations, with population-specific insights elucidating ethnic variability in symptomatology and genetic profiles. Recent case studies, including a novel compound heterozygous variant, further illustrate the complexity of the genotype-phenotype correlations. Emerging therapeutic approaches, such as enzyme replacement therapy and adeno-associated virus-mediated gene therapy, demonstrate promising potential for restoring neuraminidase-1 function and improving outcomes in preclinical models. This review emphasizes the critical role of genetic analysis in diagnosis and management while advocating for continued research into the molecular mechanisms underlying sialidosis to enable the development of targeted, personalized treatments.