뮤코다당증 진단과 치료의 최신 지견

맹세현,진동규,Maeng, Se-Hyun,Jin, Dong Kyu 대한유전성대사질환학회 2012 대한유전성대사질환학회지 Vol.12 No.2

미숙아에서 인공호흡기 치료 중 발생한 긴장성공기심장막증 2예

박원순,맹세현,서현주,신정희,정지미,김진규,유혜수,안소윤,김은선,장윤실 대한신생아학회 2011 Neonatal medicine Vol.18 No.1

Pneumopericardium is a rare form of neonatal air leakage. Tension pneumopericardium is much more infrequent, but can cause a cardiovascular deterioration with high mortality up to 80% and neurodevelopmental morbidity in half of the cases. We report two cases of preterm infants who successfully recovered from tension pneumopericardium that developed during mechanical ventilator assistance. The patients displayed a sudden increase in oxygen demand and subsequent cardiovascular deterioration. Immediate needle aspiration of the pneumopericardium performed after checking X-ray images rescued each of patient. Since the clinical symptoms are non-specific, clinicians’ suspicion is most important when patients show sudden refractory cardiovascular collapse,especially in ventilator-assisted neonates. This life threatening complication demands instant diagnosis and intervention.

Clinical, radiologic, and genetic features of Korean patients with Mucopolysaccharidosis IVA

이나희,조성윤,맹세현,전태연,손영배,김수진,박형두,진동규 대한소아청소년과학회 2013 Clinical and Experimental Pediatrics (CEP) Vol.56 No.3

Purpose Mucopolysaccharidosis IVA (MPS IVA; Morquio A syndrome) is rare lysosomal storage disorder caused by N-acetylgalactosamine-6-sulfatase (GALNS) deficiency. Only a few MPS IVA cases have been reported in the Korean literature; there is a paucity of research about clinical or radiologic findings for this disorder. Therefore, we studied clinical findings, radiological features, and genetic data of Korean MPS IVA patients for determining factors that may allow early diagnosis and that may thus improve the patients' quality of life. Method MPS IVA was confirmed via assay for enzymatic activity of leukocytes in 10 patients. The GALNS gene was analyzed. Patients' charts were retrospectively reviewed for obtaining clinical features and evaluated for radiological skeletal surveys, echocardiography, pulmonary function test, and ophthalmologic test results. Result Nine patients had severe clinical phenotype, and 1 had an intermediate phenotype, on the basis of clinical phenotype criteria. Radiologic findings indicated skeletal abnormalities in all patients, especially in the hips and extremities. Eight patients had an odontoid hypoplasia, and 1 showed mild atlantoaxial subluxation and cord myelopathy. Genetic analysis indicated 10 different GALNS mutations. Two mutations, c.451C>A and c.1000C>T, account for 37.5% (6/16) and 25% (4/16) of all mutations in this samples, respectively. Conclusion An understanding of the clinical and radiological features involved in MPS IVA may allow early diagnosis of MPS IVA. Adequate evaluations and therapy in the early stages may improve the quality of life of patients suffering from skeletal abnormalities and may reduce life-threatening effects of atlantoaxial subluxation.

A novel MLL2 gene mutation in a Korean patient with Kabuki syndrome

김수진,조성윤,맹세현,손영배,김수진,기창석,진동규 대한소아청소년과학회 2013 Clinical and Experimental Pediatrics (CEP) Vol.56 No.8

Kabuki syndrome (KS) is a rare genetic disease with a distinctive dysmorphic face, intellectual disability,and multiple congenital abnormalities. KS is inherited in an autosomal dominant manner. As the primary cause of KS, MLL2 mutations have been identified in 56–76% of affected individuals who have been tested,suggesting that there may be additional genes associated with KS. Recently, a few KS individuals have been found to have de novo partial or complete deletions of an X chromosome gene, KDM6A , which encodes a histone demethylase that interacts with MLL2 . Nevertheless, mutations in MLL2 are the major cause of KS. Although there are a few reports of KS patients in Korea, none of these had been confirmed by genetic analysis. Here, we report a case of a Korean patient with clinical features of KS. Using direct sequencing,we identified a frameshift heterozygous mutation for MLL2 : (c.5256_5257delGA;p.Lys1753Alafs*34). Clinically, the patient presented with typical facial features, and diagnosis of KS was based on the diagnostic criteria. While KS is a rare disease, other malformations that overlap with those found in individuals with KS are common. Hence, the diagnosis of KS by mutational analysis can be a valuable method for patients with KS-like syndromes. Furthermore, in the near future, other genes could be identified in patients with KS without a detectable MLL2 mutation.

Growth Hormone Treatment and Its Effect on Height in Pediatric Patients with Different Genotypes of Prader-Willi Syndrome

권차희,조성윤,맹세현,정유진,진동규 대한소아내분비학회 2012 Annals of Pediatirc Endocrinology & Metabolism Vol.17 No.3

Purpose: Differences in phenotypes between the two most common subtypes of Prader-Willi syndrome (PWS) indicate that a distinct response to growth hormone (GH)treatment may exist. To test this hypothesis, we compared the results of GH treatment in individuals with PWS due to uniparental disomy (UPD) to those of individuals with deletions. Methods: Sixty-five children with PWS who had been treated with GH for more than two years were included in this study. Twenty-one individuals were confirmed as having UPD and 44 individuals had a deletion. Height, body weight, body mass index (BMI), and insulin like growth factor-1 (IGF-I) measurements were recorded before GH treatment and at intervals of 12 months thereafter. Results: After two years of GH therapy, no significant differences were noted for yearly improvements in height standard deviation scores (SDS) between the groups (second year SDS, 0.93 ± 0.94; deletion, 0.84 ± 1.31; UPD, P = 0.717). Body weight SDS, BMI SDS,and IGF-I SDS also showed no differences between the two groups. Conclusion: Our study showed no significant differences in yearly improvements in height SDS between the deletion and UPD groups, at least for the first two years.

Osteogenesis Imperfecta Type VI with Severe Bony Deformities Caused by Novel Compound Heterozygous Mutations in SERPINF1

조성윤,기창석,손영배,김수진,맹세현,진동규 대한의학회 2013 Journal of Korean medical science Vol.28 No.7

Osteogenesis imperfecta (OI) comprises a heterogeneous group of disorders characterized by bone fragility, frequent fractures, and low bone mass. Dominantly inherited COL1A1 or COL1A2 mutations appear to be causative in the majority of OI types, but rare recessively inherited genes have also been reported. Recently, SERPINF1 has been reported as another causative gene in OI type VI. To date, only eight SERPINF1 mutations have been reported and all are homozygous. Our patient showed no abnormalities at birth, frequent fractures,osteopenia, and poor response on pamidronate therapy. At the time of her most recent evaluation, she was 8 yr old, and could not walk independently due to frequent lowerextremity fractures, resulting in severe deformity. No clinical signs were seen of hearing impairment, blue sclera, or dentinogenesis imperfecta. In this study, we describe the clinical and radiological findings of one Korean patient with novel compound heterozygous mutations (c.77dupC and c.421dupC) of SERPINF1.

Characterization of a Mucolipidosis Type II Mouse Model and Therapeutic Implication of Lysosomal Enzyme Enriched Fraction Derived from Placenta

조성윤,김기용,김수진,손영배,맹세현,김치화,고아라,송정한,여성희,김경효,진동규,Cho, Sung Yoon,Kim, Ki-Yong,Kim, Su Jin,Sohn, Young Bae,Maeng, Se Hyun,Kim, Chi Hwa,Ko, Ah-Ra,Song, Junghan,Yeau, Sung-Hee,Kim, Kyung-Hyo,Jin, Dong-Kyu The Korean Society of Inherited Metabolic Disease 2012 대한유전성대사질환학회지 Vol.12 No.1

I 세포 질환(뮤코지방증 2형; MIM 252500)과 pseudo-Hurler polydystrophy (뮤코지방증 3형; MIM 252600)는 세포내 비정상적인 리소좀 관련 운송으로 인해 발병한다. 특징적인 소견으로는 섬유아 세포의 세포질에 다수의 봉입체, 뮤코다당뇨의 부재, 혈청 내 리소좀 효소 활성도의 증가, GlcNAc-phosphotransferase 활성도의 감소를 보인다. 이 연구에서는 GlcNAc-phosphotransferase 알파/베타 아형에 대한 knockout 마우스의 표현형과 생화학적 특징을 조사하였다. 또한, 태반으로부터 추출한 리소좀 농축 분획을 knockout 마우스에 투여하였을 때 체중 증가에 대한 효과를 볼 수 있는지에 대해 알아보고자 하였다. knockout 마우스는 뮤코지방증 2형 환자에서 그렇듯이 정상적인 체중 증가를 보이지 않았고 낮은 골밀도를 보였다. 게다가 knockout 마우스의 피부 섬유 아세포의 배양액에서는 리소좀 효소 활성도가 증가한 반면, 세포 내에서는 리소좀 효소 활성도가 감소되어 있는 것을 확인할 수 있었으며 이러한 특징은 뮤코지방증 2형 환자에서 볼 수 있는 특징과 일치한다. knockout 마우스의 꼬리 정맥내로 태반에서 추출한 리소좀 농축 분획을 투여한 결과, 체중이 증가하는 것을 확인할 수 있었고, 반면 생리식염수를 투여한 knockout 마우스의 경우는 체중이 증가하지 않았다. 결론적으로, knockout 마우스의 표현형과 생화학적 특징이 뮤코지방증 2형 환자와 유사하다는 것을 확인하였으며, 리소좀 농축 분획의 치료적 가능성을 증명하였다. 더 큰 범위의 동물 실험을 진행할 필요가 있으나, 이 연구는 질병에 대한 동물 모델을 개발하고 리조솜 농축 분획의 치료적 가능성을 제시하는 것을 통해 현재까지 치료가 불가능한 뮤코지방증 2형의 새로운 치료 방법의 가능성을 열었다고 볼 수 있다. I-cell disease (mucolipidosis type II; MIM 252500) and pseudo-Hurler polydystrophy (mucolipidosis type III; MIM 252600) are disorders caused by abnormal lysosomal transport in cells. The presence of numerous inclusion bodies in the cytoplasm of fibroblasts, a lack of mucopolysacchariduria, increased lysosomal enzyme activity in serum, and decreased GlcNAc-phosphotransferase activity are hallmark. Here, we attempted to investigate phenotypical and biochemical characteristics of the knockoutmouse of GlcNAc-phosphotransferase ${\alpha}/{\beta}$ subunits; in addition, we also attempted to determine whether the lysosome enriched fraction derived from placenta can be beneficial to phenotype and biochemistry of the knockout mouse.We found that the knockout mouse failed to thrive and had low bone density, as is the case in human. In addition, skin fibroblasts from the animal had the same biochemical characteristics, including increased lysosomal enzyme activity in the culture media, in contrast to the relatively low enzyme activity within the cells. Intravenous injection of the lysosome rich fraction derived from placenta into the tail vein of the animal resulted in a gain of weight, while saline injected animals didn't.In conclusion, our study demonstrated the phenotypical and biochemical similarities of the knockout mouse to a mucolipidosis type II patient and showed the therapeutic potential of the lysosome enriched fraction. We admit that a larger scale animal study will be needed; however, the disease model and the therapeutic potential of the lysosome enriched fraction will highlight the hope for a novel treatment approach to mucopolipidosis type II, for which no therapeutic modality is available.

방광암 치료를 위한 나노의약품

송채은(Cheeun Song),장승주(Seung Ju Jang),전우혁(Woo Hyeok Jeon),맹세정(Sejung Maeng),태종현(Jong Hyun Tae),장인호(In Ho Chang) 대한비뇨기종양학회 2022 대한비뇨기종양학회지 Vol.20 No.4

Effect of Enzyme Replacement Therapy on Growth in Korean Patients with Mucopolysaccharidosis Type I

허림,조성윤,장미선,이지은,권영희,김수진,손영배,박성원,맹세현,권은경,한선주,정주연,진동규,Huh, Rimm,Cho, Sung Yoon,Chang, Mi Sun,Lee, Jieun,Kwun, Younghee,Kim, Su Jin,Sohn, Young Bae,Park, Sung Won,Maeng, Se Hyun,Kwon, Eun-Kyung,Han, Sun J The Korean Society of Inherited Metabolic Disease 2013 대한유전성대사질환학회지 Vol.13 No.2

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 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.

골 전이성 전립선암의 동물 모델

전우혁(Woo Hyeok Jeon),송채은(Cheeun Song),장승주(Seung Ju Jang),맹세정(Sejung Maeng),장인호(In Ho Chang),태종현(Jong Hyun Tae) 대한비뇨기종양학회 2022 대한비뇨기종양학회지 Vol.20 No.4