Lee, Ok-Jeong
(Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine)
,
Kim, Su-Jin
(Center of Pediatric Oncology, National Cancer Center)
,
Sohn, Young-Bae
(Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine)
,
Park, Hyung-Doo
(Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine)
,
Lee, Soo-Youn
(Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine)
,
Kim, Chi-Hwa
(Clinical Research Center, Samsung Biomedical Research Institute)
,
Ko, Ah-Ra
(Clinical Research Center, Samsung Biomedical Research Institute)
,
Yook, Yeon-Joo
(Clinical Research Center, Samsung Biomedical Research Institute)
,
Lee, Su-Jin
(Clinical Research Center, Samsung Biomedical Research Institute)
,
Park, Sung-Won
(Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine)
,
Kim, Se-Hwa
(Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine)
,
Cho, Sung-Yoon
(Department of Pediatrics, Samsung Medical Center, Sungkyunkwan Univ)
,
Kwon, Eun-Kyung
,
Han, Sun-Ju
,
Jin, Dong-Kyu
Purpose: Mucopolysaccharidosis type II (MPS II or Hunter syndrome) is a rare lysosomal storage disorder caused by iduronate-2-sulfatase (IDS) deficiency. MPS II causes a wide phenotypic spectrum of symptoms ranging from mild to severe. IDS activity, which is measured in leukocyte pellets or fibrobla...
Purpose: Mucopolysaccharidosis type II (MPS II or Hunter syndrome) is a rare lysosomal storage disorder caused by iduronate-2-sulfatase (IDS) deficiency. MPS II causes a wide phenotypic spectrum of symptoms ranging from mild to severe. IDS activity, which is measured in leukocyte pellets or fibroblasts, was reported to be related to clinical phenotype by Sukegawa-Hayasaka et al. Measurement of residual plasma IDS activity using a fluorometric assay is simpler than conventional measurements using skin fibroblasts or peripheral blood mononuclear cells. This is the first study to describe the relationship between plasma IDS activity and clinical phenotype of MPS II. Methods: We hypothesized that residual plasma IDS activity is related to clinical phenotype. We classified 43 Hunter syndrome patients as having attenuated or severe disease types based on clinical characteristics, especially intellectual and cognitive status. There were 27 patients with the severe type and 16 with the attenuated type. Plasma IDS activity was measured by a fluorometric enzyme assay using 4-methylumbelliferyl- ${\alpha}$-iduronate 2-sulphate. Results: Plasma IDS activity in patients with the severe type was significantly lower than that in patients with the attenuated type ($p$=0.006). The optimal cut-off value of plasma IDS activity for distinguishing the severe type from the attenuated type was 0.63 $nmol{\cdot}4hr^{-1}{\cdot}mL^{-1}$. This value had 88.2% sensitivity, 65.4% specificity, and an area under receiver-operator characteristics (ROC) curve of 0.768 (ROC curve analysis; $p$=0.003). Conclusion: These results show that the mild phenotype may be related to residual lysosomal enzyme activity.
Purpose: Mucopolysaccharidosis type II (MPS II or Hunter syndrome) is a rare lysosomal storage disorder caused by iduronate-2-sulfatase (IDS) deficiency. MPS II causes a wide phenotypic spectrum of symptoms ranging from mild to severe. IDS activity, which is measured in leukocyte pellets or fibroblasts, was reported to be related to clinical phenotype by Sukegawa-Hayasaka et al. Measurement of residual plasma IDS activity using a fluorometric assay is simpler than conventional measurements using skin fibroblasts or peripheral blood mononuclear cells. This is the first study to describe the relationship between plasma IDS activity and clinical phenotype of MPS II. Methods: We hypothesized that residual plasma IDS activity is related to clinical phenotype. We classified 43 Hunter syndrome patients as having attenuated or severe disease types based on clinical characteristics, especially intellectual and cognitive status. There were 27 patients with the severe type and 16 with the attenuated type. Plasma IDS activity was measured by a fluorometric enzyme assay using 4-methylumbelliferyl- ${\alpha}$-iduronate 2-sulphate. Results: Plasma IDS activity in patients with the severe type was significantly lower than that in patients with the attenuated type ($p$=0.006). The optimal cut-off value of plasma IDS activity for distinguishing the severe type from the attenuated type was 0.63 $nmol{\cdot}4hr^{-1}{\cdot}mL^{-1}$. This value had 88.2% sensitivity, 65.4% specificity, and an area under receiver-operator characteristics (ROC) curve of 0.768 (ROC curve analysis; $p$=0.003). Conclusion: These results show that the mild phenotype may be related to residual lysosomal enzyme activity.
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가설 설정
However, no study about the relationship between plasma IDS activity and clinical phenotypes of MPS II patients has been conducted. If the relationship exists, we can hypothesize that the mild phenotype may result from some residual activities of the lysosomal enzymes. Our study is the first to describe the relationship between plasma IDS activity measured with a fluorimetric enzyme assay and MPS II clinical phenotypes.
In conclusion, the relationship between clinical phenotypes of MPS II patients and plasma IDS activity exits. Therefore we can hypothesize that the mild phenotype may result from some residual activities of the lysosomal enzymes.
대상 데이터
MPS II was tentatively diagnosed based on clinical findings as well as abnormal excretion of urinary glycosaminoglycan. Genetic tests as well as enzyme assays using leukocyte pellets were used to confirm the diagnosis of 43 patients. Mutations of IDS were identified in all cases.
In this study, the plasma IDS activities of 43 male patients with MPS II were measured. Our study found a statistically significant difference in plasma IDS activities according to different clinical phenotypes of MPS II patients.
This study conducted on total 43 male patients with MPS II. Twenty-six patients (60.
We included 43 male patients with MPS II who were diagnosed at the Samsung Medical Center between April 1995 and May 2011. All patients or their parents and legal representatives provided written informed consent.
이론/모형
Plasma IDS activity was measured with a fluorimetric enzyme assay using 4-methylumbelliferyl-α-iduronate 2-sulphate according to the method by Voznyi et al.9).
성능/효과
9) developed a fluorimetric enzyme assay o measure IDS activity in fibroblasts, leukocytes, and plasma. Aside from being specific and sensitive, the IDS assay used in this study is less cumbersome and labor-intensive compared to assays using radiolabelled disaccharide. In particular, measuring residual plasma enzyme activity is a simpler method than examining skin fibroblasts or peripheral blood mononuclear cells.
In conclusion, the relationship between clinical phenotypes of MPS II patients and plasma IDS activity exits. Therefore we can hypothesize that the mild phenotype may result from some residual activities of the lysosomal enzymes.
Receiver-operator characteristic (ROC) curves for different cut-off values of plasma iduronate-2-sulfatase (IDS) activity in mucopolysaccharidosis type II patients. The optimal cut-off value of plasma IDS activity that can differentiate the severe type from the attenuated type was found to be 0.63 nmol/4 hr/mL with 88.2% sensitivity, 65.4% specificity, and an area under the ROC curve of 0.768 (95% confidence interval; P=0.003).
참고문헌 (13)
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