목적: I형 뮤코다당증 (MPS I)은 ${\alpha}$-L-iduronidase 효소의 결핍으로 인하여 발생하는 리소좀 축적 질환으로, 광범위한 양상으로 다기관에 영향을 미친다. 저신장과 성장 속도의 감소는 MPS I의 중요한 특징이다. 본 연구에서는 효소 보충 요법이 MPS I 환자들의 성장에 미치는 효과에 대해 알아보기 위하여 단일 기관의 환자들을 대상으로 분석하였다. 방법: 2세에서 15세 사이에 효소 보충 요법을 시작하여 최소 3년 이상의 치료를 시행 받은 10명의 한국 MPS I 환자들의 키 측정치를 후향적으로 분석하였다. 효소 보충 요법 시작시의 평균 나이는 7년 7개월 이였으며, 남아는 6명, 여아는 4명 이였다. 키는 표준 편차(SDS)로 표현되었다. 효소 보충 요법 전과 후의 연간 성장 속도를 계산하였으며, 구분회귀모델을 이용하여 치료 전과 후의 키 z-score를 분석하였다. 표현형[(중증(Hurler) versus 경증(Hurler-Scheie, Scheie)]이 성장에 미치는 영향에 대해서는 개별 분석을 시행하였다. 결과: 효소 보충 요법 전 1년 동안의 연간 성장은 3.3 cm (z-score=-0.21) 였으며, 효소 보충 요법 후 1년, 2년, 3년에서는 각각 6.2 cm (z-score=0.17), 5.8 cm (z-score=0.07), 3.8 cm (z-score=-0.4)이였다. 회귀분석 결과, 효소 보충 요법 전에 비하여 치료 후 기울기에 유의한 호전을 보였다(기울기 차이=0.04; P=0.022). 중증과 경증 표현형 간의 치료 전(P=0.001)과 후(P<0.0001)의 기울기 차이는 통계적으로 유의하였으나, 표현형에 따라 분석하였을 때 통계적으로 유의한 차이는 보이지 않았다. 결론: MPS I 환자들의 키 성장에 있어 aldurazyme 효소 보충 요법이 긍정적인 효과를 미치는 것으로 보인다.
목적: I형 뮤코다당증 (MPS I)은 ${\alpha}$-L-iduronidase 효소의 결핍으로 인하여 발생하는 리소좀 축적 질환으로, 광범위한 양상으로 다기관에 영향을 미친다. 저신장과 성장 속도의 감소는 MPS I의 중요한 특징이다. 본 연구에서는 효소 보충 요법이 MPS I 환자들의 성장에 미치는 효과에 대해 알아보기 위하여 단일 기관의 환자들을 대상으로 분석하였다. 방법: 2세에서 15세 사이에 효소 보충 요법을 시작하여 최소 3년 이상의 치료를 시행 받은 10명의 한국 MPS I 환자들의 키 측정치를 후향적으로 분석하였다. 효소 보충 요법 시작시의 평균 나이는 7년 7개월 이였으며, 남아는 6명, 여아는 4명 이였다. 키는 표준 편차(SDS)로 표현되었다. 효소 보충 요법 전과 후의 연간 성장 속도를 계산하였으며, 구분회귀모델을 이용하여 치료 전과 후의 키 z-score를 분석하였다. 표현형[(중증(Hurler) versus 경증(Hurler-Scheie, Scheie)]이 성장에 미치는 영향에 대해서는 개별 분석을 시행하였다. 결과: 효소 보충 요법 전 1년 동안의 연간 성장은 3.3 cm (z-score=-0.21) 였으며, 효소 보충 요법 후 1년, 2년, 3년에서는 각각 6.2 cm (z-score=0.17), 5.8 cm (z-score=0.07), 3.8 cm (z-score=-0.4)이였다. 회귀분석 결과, 효소 보충 요법 전에 비하여 치료 후 기울기에 유의한 호전을 보였다(기울기 차이=0.04; P=0.022). 중증과 경증 표현형 간의 치료 전(P=0.001)과 후(P<0.0001)의 기울기 차이는 통계적으로 유의하였으나, 표현형에 따라 분석하였을 때 통계적으로 유의한 차이는 보이지 않았다. 결론: MPS I 환자들의 키 성장에 있어 aldurazyme 효소 보충 요법이 긍정적인 효과를 미치는 것으로 보인다.
Purpose: Mucopolysaccharidosis type I (MPS I) is a lysosomal storage disorder caused by deficiency of the enzyme ${\alpha}$-L-iduronidase, which leads to a broad spectrum of multisystemic manifestations. Short stature and decreased growth velocity are prominent features of MPS I. The aim ...
Purpose: Mucopolysaccharidosis type I (MPS I) is a lysosomal storage disorder caused by deficiency of the enzyme ${\alpha}$-L-iduronidase, which leads to a broad spectrum of multisystemic manifestations. Short stature and decreased growth velocity are prominent features of MPS I. The aim of the present study was to evaluate the effect of enzyme replacement therapy (ERT) on growth of Korean MPS I patients from a single center. Methods: Height data were obtained by retrospective chart review of 10 Korean patients with MPS I who had received ERT for a minimum of 3 years. Height was expressed as standard deviation scores (SDS) based on normative data. Annual growth rates were calculated before and during ERT. A piecewise regression model was used to analyze height z-scores before and after treatment. Individual analysis was performed for impact of phenotype [(severe (Hurler) versus attenuated (Hurler-Scheie, Scheie)] on growth. Results: Annual growth was 3.3 cm (z-score= -0.21) in the year before ERT and 6.2 cm (z-score= 0.17), 5.8 cm (z-score= 0.07), and 3.8 cm (z-score= -0.4) in the first, second, and third years of ERT, respectively. Regression analysis showed improvement in the slope after ERT (difference= 0.04; P=0.022). Estimated slope differences between severe and attenuated phenotypes were statistically significant before (P=0.001) and after treatment (P<0.0001), although no significant difference was noted when stratified by phenotype. Conclusion: ERT with aldurazyme appears to have a positive impact on linear growth in patients with MPS I.
Purpose: Mucopolysaccharidosis type I (MPS I) is a lysosomal storage disorder caused by deficiency of the enzyme ${\alpha}$-L-iduronidase, which leads to a broad spectrum of multisystemic manifestations. Short stature and decreased growth velocity are prominent features of MPS I. The aim of the present study was to evaluate the effect of enzyme replacement therapy (ERT) on growth of Korean MPS I patients from a single center. Methods: Height data were obtained by retrospective chart review of 10 Korean patients with MPS I who had received ERT for a minimum of 3 years. Height was expressed as standard deviation scores (SDS) based on normative data. Annual growth rates were calculated before and during ERT. A piecewise regression model was used to analyze height z-scores before and after treatment. Individual analysis was performed for impact of phenotype [(severe (Hurler) versus attenuated (Hurler-Scheie, Scheie)] on growth. Results: Annual growth was 3.3 cm (z-score= -0.21) in the year before ERT and 6.2 cm (z-score= 0.17), 5.8 cm (z-score= 0.07), and 3.8 cm (z-score= -0.4) in the first, second, and third years of ERT, respectively. Regression analysis showed improvement in the slope after ERT (difference= 0.04; P=0.022). Estimated slope differences between severe and attenuated phenotypes were statistically significant before (P=0.001) and after treatment (P<0.0001), although no significant difference was noted when stratified by phenotype. Conclusion: ERT with aldurazyme appears to have a positive impact on linear growth in patients with MPS I.
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문제 정의
This is the first study to report the impact of ERT on linear growth in Asian patients with MPS I. The data evaluated in this study represent the patient population from a single center and the same height measuring methods were applied to all patients; thus, the height changes recorded for the patients should be relatively accurate.
제안 방법
All patients enrolled in this study were diagnosed with MPS I by biochemical determination of deficiency in IDUA enzyme activity in skin fibroblasts or peripheral blood leukocytes. In addition, molecular analysis of the IDUA gene was performed.
4 years. All patients presented with typical clinical characteristics of MPS I, such as corneal clouding, joint stiffness, and coarse facial features. Of the 10 patients, 6 were male and 4 were female.
Further calculations included mean changes in the patients’ heights and z-scores (±SD) from baseline and annual growth velocity from the year before ERT to 3 years after ERT.
Height measurements were made with standard techniques using a stadiometer (accuracy to 1 mm). Initiation of treatment ±1 month was defined as “Start of ERT.
Standardized height data (z-scores) from 24 months before and after the start of ERT were analyzed using a piecewise regression and a mixed model. The patients were individually analyzed to assess the impact of clinical phenotype (severe versus attenuated) on growth.
To our knowledge, no data are presently available for Asian MPS I patients. The objective of this retrospective study was to analyze the effect of ERT on growth patterns in 10 Korean MPS I patients with different phenotypes and to assess differences in growth at the time prior to ERT and after a minimum of 3 years of treatment with aldurazyme.
Standardized height data (z-scores) from 24 months before and after the start of ERT were analyzed using a piecewise regression and a mixed model. The patients were individually analyzed to assess the impact of clinical phenotype (severe versus attenuated) on growth.
대상 데이터
All 10 patients were born at term and were diagnosed as having MPS I at the median age of 4.4 years. All patients presented with typical clinical characteristics of MPS I, such as corneal clouding, joint stiffness, and coarse facial features.
All patients presented with typical clinical characteristics of MPS I, such as corneal clouding, joint stiffness, and coarse facial features. Of the 10 patients, 6 were male and 4 were female. Three patients were classified as Hurler, 6 as Hurler-Scheie, and 1 as Scheie.
Overall analysis was performed with height zscores of the 10 patients. The analysis showed that the slope of the regression after treatment was significantly different when compared with the slope before treatment (the estimated slopes before and after treatment were -0.
Participants were recruited from the Department of Pediatrics, Samsung Medical Center. The Institute Review Board Committee at the Samsung Medical Center approved this study and patients, parents, or legal guardians provided informed consent.
” Patients included in the analysis had more than one height measurement in the 24 month period before and after treatment. The final study population consisted of 10 patients; 6 males and 4 females.
The patients started ERT between the ages of 2 years 3 months and 14 years 10 months (median age of starting ERT was 7.7 years). Table 1 lists the demographic information, molecular characteristics, and clinical phenotypes of the patients.
In addition, molecular analysis of the IDUA gene was performed. This study included patients who had started ERT with aldurazyme between the ages of 2 and 15 years. Patients received weekly intravenous infusions of aldurazyme at 100 U/kg (0.
(Fig. 3) Two patients in our analysis (P4, P8) commenced ERT after pubertal age (14 years and 14 years 10 months, respectively). P4, who was diagnosed with Scheie syndrome, had a height SDS of -2.
성능/효과
Statistical analysis did not indicate a significant difference when comparing the z-scores at the start of ERT between the 2 groups; however, the small sample sizes probably contributed to this lack of statistical significance and acted as a confounding factor. Estimated slopes of regression for pre and post treatment of both groups showed significant differences, with height deficit in the severe group more pronounced both before and after treatment, when compared with the attenuated group. The impact of ERT on growth in patients with the severe phenotype is likely to be diminished due to their more severe skeletal dysplasia with earlier bone and joint deformities and the further progression of their multiorgan dysfunction when compared with the patients with the attenuated phenotype5).
For the whole sample (n=10; age range at start of ERT, 2 years 3 months-14 years 10 months), the height at initiation of ERT ranged from 85 to 142.6 cm (median, 100.5 cm). The mean height SDS at the start of ERT was -2.
The mean increases in the measured parameters also did not differ significantly between male and female patients during the first 3 years of life, and because our sample size was small, we did not perform any analyses by gender. Natural growth patterns for MPS I patients which are also important in evaluating the effect of ERT on growth, are difficult to obtain due to the rare incidence of the disease and ethical factors related with treatment initiation after diagnosis of MPS I.
In conclusion, the present data show an overall increase in growth after the initiation of ERT with aldurazyme
. This indicates a positive impact of ERT on growth in patients with MPS I who without ERT would otherwise have shown more marked growth retardation.
This is the first study to report the impact of ERT on linear growth in Asian patients with MPS I. The data evaluated in this study represent the patient population from a single center and the same height measuring methods were applied to all patients; thus, the height changes recorded for the patients should be relatively accurate. All the patients are of the same ethnicity, so the data are unlikely to be confounded by ethnic differences.
27 2 years after ERT. The patients showed an overall improvement in growth after ERT, although phenotypic differences were seen. (Fig.
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