한국인 제2형 뮤코다당증 5명 환자의 생화학적, 분자유전학적, 임상적 특징
Biochemical, molecular, and clinical characteristics of five Korean patients with Mucopolysaccharidosis type II
Abstract
Objective: Mucopolysaccharidosis type II (MPS II) is a rare disorder caused by a deficiency in lysosomal enzyme iduronate-2-sulfatase (IDS). The mutation spectrum of this disorder is heterogeneous, which complicates the molecular diagnosis of MPS II. We aimed to determine the clinical, biochemical and genetic data, including two novel IDS gene mutations, in patients with MPS II. Methods: Biochemical and clinical findings were investigated and mutations in the IDS gene were identified using direct sequencing method in five patients with MPS II with high glycosaminoglycan (GAG) levels. Results: We identified five patients with MPS II by enzyme IDS and molecular analysis of the IDS gene. All patients had elevated GAG levels, but no clear correlation was found between urinary GAG levels and phenotype. Our results indicate a relation between disease severity and residual enzyme activity. In this study, 4 mutations in 5 Korean patients with MPS II are reported; 2 missense, one insertion, and two IDS-IDS2 recombination mutations. Of these mutations, 2 are novel, that is, 1 small insertion mutation (p.Thr409Hisfs*22) and 1 missense mutation (p.Gly134Glu). In patients with the attenuated phenotype (3 of the 5 patients), missense mutations and small insertion mutation were identified. Two patients with the IDS-IDS2 recombination mutation had the severe MPS II phenotype. Most patients, including an adult with MPS II, showed several clinical improvements after enzyme replacement therapy. Conclusion: The results of this study expand our better understanding of the clinical and molecular characteristics and the global pool of patients with MPS II.