Clinical and Genetic Landscapes of Mucopolysaccharidosis Type III in 20 Chinese Patients

Background: Mucopolysaccharidosis type III (MPS III), also known as Sanfilippo syndrome, is a devastating lysosomal storage disorder characterized by severe, progressive neurodegeneration. Diagnosing this condition is challenging because early somatic signs are often mild, frequently leading to misdiagnosis as autism spectrum disorder or attention-deficit/hyperactivity disorder. As the subtype distribution and genetic mutation spectrum show significant ethnic heterogeneity, population-specific data are essential for accurate clinical management. This study aimed to investigate the clinical features, biochemical indicators, and genetic landscape of 20 Chinese patients (10 with type IIIA and 10 with type IIIB) to improve early recognition and diagnostic accuracy. Phenotypes and genotypes were summarized using urinary glycosaminoglycan levels, lysosomal enzyme activity assays, and whole-exome sequencing. Methods: A retrospective analysis was conducted on 20 patients with MPS III (10 with type IIIA and 10 with type IIIB). Urinary glycosaminoglycan (GAG) levels, lysosomal enzyme activities in peripheral blood leukocytes, and genetic analysis using whole-exome sequencing (WES) were performed to summarize their phenotypes and genotypes. Results: All 20 patients exhibited progressive neurodegeneration, with initial symptoms primarily including delayed language development (100%) and cognitive regression, accompanied by varying degrees of hyperactivity, sleep disorders, and coarse facial features. Biochemical data showed significantly elevated urinary GAG excretion in all patients, with type IIIA patients showing markedly decreased activity of heparan N-sulfatase (SGSH) and type IIIB patients showing significantly reduced α-N-acetylglucosaminidase (NAGLU) activity. Genetic testing revealed that in the SGSH gene, c.1129C>T and c.703G>A were the most frequent mutations, while in the NAGLU gene, c.1693C>T and c.1081T>C were common mutations. Compared with European populations, the proportions of IIIA and IIIB subtypes were similar in this cohort. Conclusion: Chinese patients with MPS III exhibit significant clinical variability and delayed diagnosis. Delayed language development accompanied by mild facial dysmorphism is an important diagnostic clue. Population-specific high-frequency mutation sites exist in the SGSH and NAGLU genes, and clarifying the mutation spectrum can aid in precise genetic counseling and prenatal diagnosis.