프래더 윌리 증후군의 유전학적 발병 기전에 따른 표현형 및성장 호르몬 치료 효과에 관한 연구

배근욱,고정민,유한욱 대한소아청소년과학회 2008 Clinical and Experimental Pediatrics (CEP) Vol.51 No.3

Purpose:Prader-Willi syndrome (PWS) is a complex genetic disorder, caused by the deletion of the paternally derived 15q11-13 region or the maternal uniparental disomy of chromosome 15 (mUPD(15)). In this study, we compared phenotypic differences between those patients whose disease was caused by microdeletion and those caused by mUPD(15). In addition, a comparison of the efficacy of growth hormone (GH) therapy between these two PWS genotypes was analyzed. Methods:Fifty-three patients were diagnosed as having PWS based on molecular and cytogenetic analyses and clinical features. Data that included maternal age, birth weight, a feeding problem in the neonatal period, cryptorchidism, developmental delay or mental retardation, short stature, hypopigmentation, changes in height, weight, and body mass indexes (BMI) before and after GH treatment were obtained by a retrospective review of medical records. The data from the patients with microdeletion were compared with those from the patients with mUPD(15). Results:Of the 53 patients with genetically confirmed PWS, 39 cases had microdeletion and 14 mUPD(15). Maternal ages were significantly higher in the mUPD(15) group, and hypopigmentation and a feeding problem in the neonatal period were more frequent in the microdeletion group. Growth hormone was administered to 20 patients [14 with microdeletion, 6 with mUPD(15)]. There were no differences between the two groups in height velocity, weight and height SDS, and BMI after GH therapy. Conclusion:Phenotype and genotype correlations were observed in Korean PWS patients, such as more advanced maternal ages in the mUPD(15) group and more feeding problems and hypopigmentations in the microdeletion group. Further long-term prospective studies are needed to correlate other aspects of the phenotypes. (Korean J Pediatr 2008;51:315- 322) Purpose:Prader-Willi syndrome (PWS) is a complex genetic disorder, caused by the deletion of the paternally derived 15q11-13 region or the maternal uniparental disomy of chromosome 15 (mUPD(15)). In this study, we compared phenotypic differences between those patients whose disease was caused by microdeletion and those caused by mUPD(15). In addition, a comparison of the efficacy of growth hormone (GH) therapy between these two PWS genotypes was analyzed. Methods:Fifty-three patients were diagnosed as having PWS based on molecular and cytogenetic analyses and clinical features. Data that included maternal age, birth weight, a feeding problem in the neonatal period, cryptorchidism, developmental delay or mental retardation, short stature, hypopigmentation, changes in height, weight, and body mass indexes (BMI) before and after GH treatment were obtained by a retrospective review of medical records. The data from the patients with microdeletion were compared with those from the patients with mUPD(15). Results:Of the 53 patients with genetically confirmed PWS, 39 cases had microdeletion and 14 mUPD(15). Maternal ages were significantly higher in the mUPD(15) group, and hypopigmentation and a feeding problem in the neonatal period were more frequent in the microdeletion group. Growth hormone was administered to 20 patients [14 with microdeletion, 6 with mUPD(15)]. There were no differences between the two groups in height velocity, weight and height SDS, and BMI after GH therapy. Conclusion:Phenotype and genotype correlations were observed in Korean PWS patients, such as more advanced maternal ages in the mUPD(15) group and more feeding problems and hypopigmentations in the microdeletion group. Further long-term prospective studies are needed to correlate other aspects of the phenotypes. (Korean J Pediatr 2008;51:315- 322)

소아에서 스테로이드 반응성 신증후군의 관해기에 발병한 Kimura 병의 1례

배근욱,이민규,이주훈,허주영,박영서,Bae Keun-Wook,Lee Min-Kyu,Lee Joo-Hoon,Huh Joo-Ryung,Park Young-Seo 대한소아신장학회 2006 Childhood kidney diseases Vol.10 No.1

저자들은 스테로이드 반응성 재발성 신증후군의 과거력이 있는 환아에서 관해기에 발병한 Kimura 병을 종괴의 전절제 후 스테로이드 및 cyclosporin 투여로 치료한 증례를 경험하고 이를 보고하는 바이다. Kimura's disease is a rare chronic inflammatory disease of unknown etiology which appears primarily in young Asian males as non-tender subcutaneous swellings in the head and neck region. Histologic characteristics are the presence of lymphoid follicles, vascular proliferation and infiltration of eosinophils. Peripheral eosinophilia and elevated serum IgE are frequently combined. Systemic steroid therapy with surgical excision is the mainstay of treatment, though recurrence after surgery or discontinued steroid treatment is common. It has been known that about 16% of the cases are associated with renal diseases, particularly nephrotic syndrome. We present an 8-year-old boy with a past history of steroid-responsive, infrequently relapsing nephrotic syndrome who developed right buccal swelling and peripheral eosinophilia during the remission state. He has been managed with surgical resection, steroid and cyclosporine due to multiple recurrences.

악안면 두개골격의 수직·수평적 부조화에 관한 두부방사선 계측학적 연구

배근욱,유영규 대한치과교정학회 1988 대한치과교정학회지 Vol.18 No.1

The purposes of the present study were to decribe the vertical and anteroposterior facial dysplasis,and to identify morphologic differences associated with various facial patterns. Anteroposterior dysplasia was classified by traditional Angle's malocclusion classfication and according to vertical relationships based on the SN-MP andgle, facial pattern ws subclassified to 3 vertical groups in each malocclusion group. Each vertical group composed of 20 samples and total 180 samples aged from 9 to 14 years. The results were as follows; 1. The skeletal differences that lead to disportionate lower facial height in vertical and andteroposterior facial dysplasia were closely related to mandibular morphology. 2. Hyperdivergent group, compared with hypodivergent group, demonstrated decrease of SNA and SNB and linguoversion of maxilliary and mandibular central incisors in asll malocclusion groups. 3. Irrespective of rotation of the jaws, Wits appraisal was a useful measurement in evalution of relative anteroposterior relationship of maxilla and mandible. 4. As SN-MP andgle increased, anterior facial height, especially lower anterior ffacial height, demonstrated significant increase and intermaxillary space also tended to increase. 5. The correlation coefficients of SN-MP angle and PTFH/ATFH demonstrated the highest value in all malocclusion groups.

A case of anemia caused by combined vitamin B12 and iron deficiency manifesting as short stature and delayed puberty

송승민,배근욱,윤회수,임호준,서종진 대한소아청소년과학회 2010 Clinical and Experimental Pediatrics (CEP) Vol.53 No.5

Anemia caused by vitamin B12 deficiency resulting from inadequate dietary intake is rare in children in the modern era because of improvements in nutritional status. However, such anemia can be caused by decreased ingestion or impaired absorption and/or utilization of vitamin B12. We report the case of an 18-yearold man with short stature, prepubertal sexual maturation,exertional dyspnea, and severe anemia with a hemoglobin level of 3.3 g/dL. He had a history of small bowel resection from 50cm below the Treitz ligament to 5 cm above the ileocecal valve necessitated by midgut volvulus in the neonatal period. Laboratory tests showed deficiencies of both vitamin B12 and iron. A bone marrow examination revealed dyserythropoiesis and low levels of hemosiderin particles, and a cytogenetic study disclosed a normal karyotype. After treatment with parenteral vitamin B12and elemental iron, both anemia and growth showed gradual improvement. This is a rare case that presented with short stature and delayed puberty caused by nutritional deficiency anemia in Korea.

치아교정 X-RAY 자동분석 SYSTEM

박영철,배근욱 의치학사 1988 치과임상 Vol.8 No.1

Topiramate can reduce the number of episodic attacks incyclic vomiting syndrome : a case report

염미선,배근욱,유수영,고태성 대한소아청소년과학회 2007 Clinical and Experimental Pediatrics (CEP) Vol.50 No.4

Cyclic vomiting syndrome (CVS) is a paroxysmal, recurrent vomiting disorder of unknown pathophysiology and target organ. It has been hypothesized that CVS shares the same mechanism as migraine. We describe here a 5-year-old boy with CVS characterized by episodic vomiting attacks. These recurrent vomiting episodes began at 3 years of age, occurred every month and lasted for 5 days at a time. At the time of admission, no abnormal physical or neurological findings were observed and laboratory findings, including brain MRI and endoscopic examination, revealed nothing specific. The vomiting episodes were self-limited but recurrent and severely interrupted his daily life. When this patient was treated with topiramate, he showed a marked increase of symptom-free periods. 주기성 구토증(cyclic vomiting syndrome, CVS)은 예측 불가능한 심한 구토가 특별한 원인 없이 시작되어 각 개인마다 일정한 임상 양상을 보이며 수 시간에서 수일간 지속되다가 저절로 호전되는 것을 반복하는 질환으로서, 그 임상 양상은 편두통과 많은 공통점을 보이며 그 병리생리학적 원인이 편두통과 유사한 것으로 추정되어지고 있다. 저자들은 만 3세 경 부터 시작된 발작적이고 반복적인 주기적 구토를 주소로 내원한 5세 남아에서 주기적 구토증을 진단하였으며, 이 환아에서 대규모의 임상 연구를 통해 단독 요법으로 편두통의 예방에 효능이 있음이 인정된 광범위 항경련제인 topiramate(TPM)를 투여하여 그 증상이 호전됨을 경험하고 이를 보고하는 바이다.

소아 IgA 신병증의 임상병리학적 양상과 예후

우성일,배근욱,이주훈,박영서,조영미 대한소아청소년과학회 2007 Clinical and Experimental Pediatrics (CEP) Vol.50 No.2

Purpose : Clinicopathological features were investigated to clarify the outcome and prognostic indicators for patients with IgA nephropathy in Korean children. Methods : We reviewed the outcomes of 61 patients in whom IgA nephropathy was diagnosed before the age of 15 years from 1991 to 2005 and followed-up at least for one year. All patients were confirmed by renal biopsy. Results : After mean follow-up of 5.2 years from onset, 24 patients of 61 (39.3%) were in clinical remission at the last examination. Thirty patients (49.2%) had hematuria or mild proteinuria (<1 g/ m2/d), five (8.2%) had severe proteinuria ( 1 g/m2/d), and two (3.3%) had chronic renal failure. By univariate analysis, initial presentation at onset and Haas classification were less concordant with outcome. Hypertension during follow-up, rather than hypertension at presentation, was significantly correlated with outcomes (P<0.01). Sixty percent of patients who had more than 20% of glomerular sclerosis or crescent progressed to severe proteinuria or chronic renal failure, as compared with 7.1% of those who did not (P<0.01). Conclusion : Prognosis of childhood IgA nephropathy had a relatively benign course during a mean follow-up of 5.2 years. Persistent hypertension during follow-up and more than 20% of glomerular sclerosis or crescent were strong predictors of a progressive course of IgA nephropathy. A new histologic classification according to characteristics of childhood IgA nephropathy must be established to assess prognosis. Further efforts should be made to understand the prognosis of IgA nephropathy through long-term follow-up. 목 적 : 소아 IgA 신병증을 발병시 임상 양상 및 병리학적으로 분류하여 이들의 임상 경과와 예후 인자를 조사하고자 한다. 방 법 : 1991년부터 2005년까지 서울아산병원 소아과에서 신생검으로 IgA 신병증으로 진단되고 1년 이상 추적 관찰한 61명의 환아를 대상으로 후향적으로 조사하였다. 결 과 : 환아들의 발병시 평균 연령은 9.3세였고, 평균 추적관찰 기간은 5.2년 이었다. 전체 61명의 환아 중 남아가 42명 여아가 19명이었다. 최종 추적 관찰시 24명(39.3%)는 정상 소견을 보였고, 30명(49.2%)은 혈뇨 또는 경도의 단백뇨(<1 g/m2/d), 5명(8.2%)은 중증도의 단백뇨( 1 g/m2/d), 2명(3.3%)은 만성 신부전을 보였다. 추적 관찰 중 지속되는 고혈압의 여부는 임상 경과와 통계적으로 유의한 상관관계가 있었다(P<0.01). Haas 분류는 임상 경과와는 상관관계가 없었다. 그러나 20% 이상의 사구체에서 전경화나 분절 경화 또는 반월체 형성이 있었던 경우 60%에서 지속적인 중증도의 단백뇨와 만성 신부전의 소견을 보여 유의한 상관관계를 보였다(P<0.01). 결 론 : 소아 IgA 신병증의 단기간의 추적 관찰 중 임상 경과 및 예후는 비교적 양호하다. 그러나 추적 관찰 중 지속적인 고혈압 및 신생검시 20% 이상의 사구체에서 전경화나 분절 경화 또는 반월체 형성이 있는 경우에서는 나쁜 예후 인자로서 유의한 상관 관계를 보였다. 앞으로 소아 IgA 신병증의 특징에 맞는 조직병리학적 분류가 필요하며, 보다 많은 소아 IgA 신병증 환아의 장기간 추적 관찰을 통한 연구가 이루어져야 할 것이다.

소아 동종조혈모세포이식을 받은 환아에서 이식 전후의 혈청 Ferritin 값의 변화와 이식 결과에 미치는 영향

이윤정,조형래,배근욱,박미림,고경남,송준섭,서종진,임호준 대한혈액학회 2009 Blood Research Vol.44 No.4

Background: Iron overload, primarily related to RBC transfusions, is a relatively common complication in hematopoietic stem cell transplant (HSCT) recipients. There are emerging data from retrospective studies that iron overload can significantly increase the risk of nonrelapse mortality after allogeneic HSCT. Methods: One hundred and five children who received allogeneic HSCT between Jan 2004 and Feb 2009 at Asan Medical Center were analyzed. For indirect estimation of body iron stores, we measured serum ferritin serially in HSCT recipients at pre-transplant, 3 months and 1 year post-transplant. We also analyzed prevalence of hyperferritinemia, correlation of iron overload and transplant-related outcomes and complications. Results: The prevalence of hyperferritinemia (≥1,000 μg/L) at pre-HSCT, 3 months and 1 year post-HSCT were 66.7% (70/105), 78% (71/91) and 40.9% (27/66), respectively. Children with hyperferritinemia (≥1,000 μg/L) at 3 months post-HSCT had worse 2-year OS (79% vs 95%; P=0.023) than those in the low ferritin group (<1,000 μg/L). Very high levels (VHL) of ferritin (≥3,000 μg/L) at 3 months post-HSCT were associated with increased incidence of treatment related mortality (23% vs 2%, P=0.001) and acute graft-versus-host disease (54% vs 26%, P=0.007) in univariate analysis. VHL of ferritin remained significant in multivariate analysis. Conclusion: Hyperferritinemia at 3 months post-HSCT had adverse impact for transplantation outcome in patients undergoing allogeneic stem cell transplantation. These results suggest that the screening and adequate treatment of iron overload in HSCT recipients might be helpful to improve the HSCT outcomes.

소아 중환자실에 입실한 소아 종양/혈액 질환 환자의 예후 및 위험인자

김보은,하은주,배근욱,김성국,임호준,서종진,박성종,박성종 대한소아청소년과학회 2009 Clinical and Experimental Pediatrics (CEP) Vol.52 No.10

Purpose:To evaluate the risk factors for mortality and prognostic factors in pediatric hemato-oncology patients admitted to the pediatric intensive care unit (PICU). Methods:We retrospectively reviewed the medical records of pediatric hemato-oncology patients admitted at the PICU of the Asan Medical Center between September 2005 and July 2008. Patients admitted at the PICU for perioperative or terminal care were excluded. Results:Total 88 patients were analyzed. Overall ICU mortality rate was 34.1%. Mean age at PICU admission was 7.0± 5.7 years and mean duration of PICU stay was 18.1±22.2 days. Hematologic diseases contributed to 77.3% of all the primary diagnoses, and the primary cause of admission was respiratory failure (39.8%). The factors related to increased mortality were C-reactive protein level (P<0.01), ventilation or dialysis requirement (P<0.01), and hematopoietic stem cell transplantation (P<0.05). In all, 3 scoring systems were investigated [Number of Organ System Failures (OSF number), the Pediatric Risk of Mortality III (PRISM III) score, and the Sequential Organ Failure Assessment (SOFA) score]; higher score correlated with worse outcome (P<0.01). The Oncological Pediatric Risk of Mortality (O-PRISM) scores of the 21 patients who had received hematopoietic stem cell transplantation were higher among the non-survivors, but not statistically significant (P=0.203). Conclusion:The PRISM III and SOFA scores obtained within 24 hours of PICU admission were found to be useful as early mortality predictors. The highest OSF number during the PICU stay was closely related to poor outcome. 목 적:최근 다양한 치료 방법의 발전과 지지요법의 발달로, 소아 종양/혈액 질환 환자의 생존율이 향상되었으나, 적극적이고 다양한 치료를 하게 되면서 이와 관련된 여러 합병증으로 소아 중환자실에 입실하는 경우 또한 많아졌다. 이에 본 연구에서는 소아 중환자실에 입실한 소아 종양/혈액 질환 환자의 임상양상과 사망률을 살펴보고, 소아 종양/혈액 질환 환자에게 적합한 중증도 측정 체계와 사망률에 영향을 미치는 위험 요인에 대해 알아보고자 했다. 방 법:2005년 9월부터 2008년 7월까지 서울아산병원 소아 중환자실에 입실한 소아 종양/혈액 질환 환자 중 3일 이상 재실한 환자를 대상으로 후향적으로 의무기록을 조사했다. 생존군과 비생존군으로 나누어 나이, 성별, 재실 일수에 대하여 조사했고, 기저 질환과 중환자실 입원 이유, 인공호흡기 적용 여부, 투석 및 승압제 투여 여부, CRP 및 ANC에 따른 사망률을 알아보았다. 또, 생존군과 비생존군의 OSF number, SOFA score, PRISM III score, O-PRISM score를 비교하고, 점수에 따른 사망률을 알아보았다. 결 과:총 88예 중 30예가 사망하여 사망률은 34.1%이었다. 남아가 49예, 여아가 39예이었고, 평균 나이는 7.0±5.7세, 평균 재원일수는 18.1±22.2일로 이었다. 기저 질환은 혈액 질환이 68예(77.3%)로 가장 많았으며, 중환자실 입실 이유는 호흡기능 부전이 35예(39.8%)로 가장 많았고, 패혈쇼크가 19예(21.6%)이었다. CRP는 생존군에서 9.1±9.0, 비생존군에서 16.4±11.2로, 비생존군에서 유의하게 높았고(P<0.01), 비생존군에서 인공호흡기 치료나 투석이 필요했던 경우가 많았으며(P<0.01), 조혈모세포 이식을 받은 군의 사망률이 유의하게 높았다(P<0.05). 중증도 측정 체계 중에서는 initial OSF number, highest OSF number, SOFA score, PRISM III score가 비생존군에서 의미 있는 증가를 보였고(P<0.01), 이들을 수용자 작업특성곡선을 사용하여 비교하였을 때, highest OSF number가 곡선하면적 0.845로 가장 높았고, 중환자실 입실 24시간 이내에 측정한 PRSIM III score와 SOFA score의 곡선하면적이 각각 0.723, 0.751로 유의한 결과를 보였다. 총 21예에서 조혈모세포 이식을 받았으며 이들의 O-PRISM score는 비생존군에서 높은 경향을 보였으나, 통계적으로 유의하지는 않았다. 결 론: 본 연구에서 소아 중환자실 입실한 소아 종양/혈액 질환 환자 사망의 위험인자로는 CRP, 인공호흡기 치료, 투석, 조혈모세포 이식이 있었으며, 예후 예측지표로는 highest OSF number, PRISIM III score, SOFA score가 의미 있는 것으로 분석되었다.

Cisplatin을 포함한 항암치료를 받은 소아에서 이독성

장희진,조형래,이재희,배근욱,서종진,문형남,임호준 대한소아청소년과학회 2010 Clinical and Experimental Pediatrics (CEP) Vol.53 No.2

Purpose:Cisplatin is highly effective for the treatment of solid tumors in children. However, the clinical use of cisplatin is limited by its ototoxicity. The aim of this study was to evaluate the ototoxicity in children treated with cisplatin. Method:We performed a single institution retrospective analysis of pediatric oncology patients who received cisplatin therapy between January 2001 and January 2008. Thirty-seven patients with sufficient medical and audiologic data were included in this study. Results:The median age at the time of diagnosis was 10.7 (range 3.8–16.7) years. There were 16 males and 21 females. The underlying diseases were osteosarcoma (15 cases), medulloblastoma (14 cases), germ cell tumors (7 cases), and hepatoblastoma (1 case). The median individual dose was 100 mg/m2/cycle (56-200). The median cumulative dose was 480 mg/m2 (200-1,490). Sixteen patients (43%) received cranial radiotherapy. Of the 37 patients, 17 developed hearing loss, leading to an overall incidence of 46%. Logistic regression showed that age at treatment (P=0.04) and cumulative dose of cisplatin (P=0.005) were the significant risk factors in predicting hearing loss in children treated with cisplatin. In all the patients who had hearing loss, there was neither improvement nor aggravation during the follow-up (3–68 months). Conclusion:The cumulative dose of cisplatin (>500 mg/m2) and younger age at treatment (<12 years) were 2 most important risk factors for ototoxicity in patients treated with cisplatin. Serial audiometric evaluations are needed in the patients with risk factors during and after cisplatin treatment. 목적:Cisplatin은 소아 고형종양의 치료에 효과적으로 사용되는 항암제이다. 그러나 이독성의 발생은 cisplatin의 사용을 제한하고 있다. 이에 저자들은 cisplatin을 투여 받은 소아 고형종양 환아에서 발생한 이독성의 특징과 관련 인자들을 알아보고자 하였다. 방법:2001년 1월부터 2008년 1월까지 서울아산병원 소아과에서 고형종양으로 cisplatin을 포함한 항암치료를 받았고, 청력검사를 시행 받은 37명의 환아를 대상으로 하였다. 대상 환아의 진단 시 나이, 성별, 진단명, 두개 방사선 조사 여부, 그리고 cisplatin의 개별용량 및 누적량을 조사하였다. 청력검사는 항암 치료 전과 종료 후에 순음청력검사를 시행하였다. 결과:37명 환아의 기저 질환은 골육종 15례, 수모세포종 14례, 생식세포종양 7례, 그리고 간모세포종 1례이었다. 진단 시 정중 연령은 10.7세(3.8-16.7)이었고 남아가 16명, 여아가 21명이었다. 투여된 cisplatin의 정중 개별용량은 100 mg/m2/cycle (56-200), 그리고 정중 누적량은 480 mg/m2 (200-1,490)이었다. 16명(43%)의 환아가 두개 방사선 조사를 받았다. 치료 종료 후 시행한 청력검사에서 청력장애를 보인 환아들은 17명(46 %)이었다. 진단 시 나이가 12세 미만인 군(P=0.04)과 cisplatin 누적량 500 mg/m2 이상인 군(P=0.005)에서 이독성의 발생이 유의하게 증가하였다. 환아의 성별, 진단명, 두개 방사선 조사 여부, 그리고 cisplatin의 개별용량과 이독성의 발생과는 유의한 차이는 없었다. 정중 22개월(3-68)의 추적관찰 기간 동안 청력장애를 보인 16명의 환아들은 장애가 호전되지 않았다. 결론:진단 시 12세 미만과 누적량 500 mg/m2 이상의 cisplatin 투여받은 환아군에서 cisplatin에 의한 이독성의 빈도가 유의하게 증가하였으며 청력장애 발생 시에는 치료 종료 후에도 호전되지 않았다. 이에 위험인자를 지닌 환아들의 주기적인 청력검사가 필요하며, 이독성 발생의 예방에 대한 연구도 필요할 것으로 생각된다.