Clinical characteristics and genotypes of 201 patients with mucopolysaccharidosis type II in China: A retrospective, observational study

Abstract Mucopolysaccharidosis type II (MPS II) is an X‐linked recessive lysosomal storage disease caused by a disease‐associated variant in the IDS gene, which encodes iduronate 2‐sulfatase (IDS). We aimed to characterize the clinical characteristics and genotypes of the largest cohort of Chinese patients with MPS II and so gain a deeper understanding of natural disease progression. Patients with confirmed MPS II and without treatment were included. The disease was classified as severe in patients with neurological impairment, and as attenuated in patients aged >6 years without neurological impairment. Of the 201 male patients, 78.1% had severe MPS II. Cognitive regression occurred before age 6 years in 94.3% of patients. Of 122 IDS variants identified, 37 were novel. Among the large gene alteration types identified, only the frequency of IDS‐IDS2 recombination was significantly higher in severe versus attenuated MPS II ( P = 0.032). Some identified point variants could inform the understanding of genotype–phenotype correlations. In conclusion, this study showed that classification of the disease as attenuated should only be made in patients aged >6 years. Our findings expand the understanding of the genotype–phenotype relationship, inform the diagnostic process, and provide an indication of the likely prognosis.