원발성 간암 119예에 대한 임상적 관찰

손영배,박창우,이영철,김영재,오용구,박인조 大韓消化器病學會 1985 大韓消化器病學會誌 Vol.17 No.1

A Case of Late-onset Episodic Myopathic Form with Intermittent Rhabdomyolysis of Very-long-chain acyl-coenzyme A Dehydrogenase (VLCAD) Deficiency Diagnosed by Multigene Panel Sequencing

손영배,안선현,장자현,이새미,Sohn, Young Bae,Ahn, Sunhyun,Jang, Ja-Hyun,Lee, Sae-Mi The Korean Society of Inherited Metabolic Disease 2019 대한유전성대사질환학회지 Vol.19 No.1

Very-long-chain acyl-CoA dehydrogenase (VLCAD) 결핍증은 상염색체 열성으로 유전되는 유전성대사질환으로 미토콘드리아에서 장쇄지방산의 산화 장애이다. VLCAD 결핍증의 임상증상은 중증도 및 발현 시기에 따라 심각한 심장 이상을 동반하는 신생아기 발현형, 소아기 발현형, 지발형의 세 가지로 분류할 수 있다. 저자들은 혈장 아실카르니틴 분석과 유전자패널 염기서열분석 방법으로 확진된 성인기 발현형 VLCAD 결핍증 1례를 경험하였기에 보고하고자 한다. 34세 여자가 반복되는 근육통증과 간헐적 횡문근융해증의 병력을 주소로 내원하였다. 환자는 12세에 처음으로 운동 후 횡문근융해증으로 급성 신부전이 발생하여 혈액 투석을 받고 회복하였다. 이후 환자는 장시간의 운동이나 금식 후에 반복적으로 근육통증과 횡문근융해증이 발생하였다. 내원 시 신체 검진과 신경학적 검진은 정상이었다. 내원시 혈장 AST/ALT, Creatinine kinase (CK)는 약간 상승해있었으나, 이전 의무기록에 의하면 횡문근융해증이 있을 당시 AST/ALT, CK는 매우 상승하였다. 환자의 병력을 토대로 지방산대사장애 의심하에 감별진단을 위하여, 유전자 패널 염기서열 분석과 혈장 아실카르니틴 분석을 시행하였다. 혈장 아실카르니틴 분석결과 C14:1 ($1.453{\mu}mol/L$; 참고치, 0.044-0.285)와 C14:2 ($0.323{\mu}mol/L$; 0.032-0.301)가 증가였고, C14 ($0.841{\mu}mol/L$; 0.065-0.920)는 높은 정상이었다. 유전자패널 염기서열분석에서는 ACADVL 유전자에서 두 개의 병원성변이가 이형접합으로 발견되었으며, 이는 Sanger 염기서열 분석으로 확진되었다: c.[1202G>A(;)1349G>A] (p.[(Ser401Asn)(;)(Arg 450His)]). 환자는 생화학적, 유전학적 검사결과를 바탕으로 지발형 VLCAD 결핍증으로 확진되어 저지방식이와 급성 대사장애를 예방하기 위한 영양 교육을 받았다. 경증의 지발형 지방산 대사장애는 임상증상과 생화학적 검사 이상이 간헐적으로 발생하기 때문에 진단이 어렵다. 유전자패널 염기서열 분석은 지방산대사 장애와 같이 임상증상과 원인 유전자 이상이 다양한 대사 이상질환에서 유용한 진단법이 될 수 있다. Very-long-chain acyl-CoA dehydrogenase (VLCAD) deficiency (OMIM#201475) is an autosomal recessively inherited metabolic disorder of mitochondrial long-chain fatty acid oxidation. The clinical features of VLCAD deficiency is classified by three clinical forms according to the severity. Here, we report a case of later-onset episodic myopathic form of VLCAD deficiency whose diagnosis was confirmed by plasma acylcarnitine analysis and" multigene panel multigene panel sequencing. A 34-year old female patient visited genetics clinic for genetic evaluation for history of recurrent myopathy with intermittent rhabdomyolysis. She suffered first episode of rhabdomyolysis with acute renal failure requiring hemodialysis at twelve years old. After then, she suffered several times of recurrent rhabdomyolysis provoked by prolonged exercise or fasting. Physical and neurologic exam was normal. Serum AST/ALT and creatinine kinase (CK) levels were mildly elevated. However, according to her previous medical records, her AST/ALT, CK were highly elevated when she had rhabdomyolysis. In suspicion of fatty acid oxidation disorder, multigene panel sequencing and plasma acylcarnitine analysis were performed in non-fasting, asymptomatic condition for the differential diagnosis. Plasma acylcarnitine analysis revealed elevated levels of C14:1 ($1.453{\mu}mol/L$; reference, 0.044-0.285), and C14:2 ($0.323{\mu}mol/L$; 0.032-0.301) and upper normal level of C14 ($0.841{\mu}mol/L$; 0.065 -0.920). Two heterozygous mutation in ACADVL were detected by multigene panel sequencing and confirmed by Sanger sequencing: c.[1202G>A(;) 1349G>A] (p.[(Ser 401Asn)(;)(Arg450His)]). Diagnosis of VLCAD deficiency was confirmed and frequent meal with low-fat diet was educated for preventing acute metabolic derangement. Fatty acid oxidation disorders have diagnostic challenges due to their intermittent clinical and laboratorial presentations, especially in milder late-onset forms. We suggest that multigene panel sequencing could be a useful diagnostic tool for the genetically and clinically heterogeneous fatty acid oxidation disorders.

자치제도비교 : 일본의 기초행정기관과 행정수요달성

손영배 한국지방행정연구원 1999 지방포럼 Vol.2 No.-

특성화고 진로교육의 과제와 방향

손영배 한국진로교육학회 2017 한국진로교육학회 학술대회지 Vol.2017 No.11

The First Korean Patient with Potocki-Shaffer Syndrome: A Rare Cause of Multiple Exostoses

손영배,임신영,조은해,김옥화 대한의학회 2015 Journal of Korean medical science Vol.30 No.2

Potocki–Shaffer syndrome (PSS, OMIM #601224) is a rare contiguous gene deletionsyndrome caused by haploinsufficiency of genes located on the 11p11.2p12. Affectedindividuals have a number of characteristic features including multiple exostoses, biparietalforamina, abnormalities of genitourinary system, hypotonia, developmental delay, andintellectual disability. We report here on the first Korean case of an 8-yr-old boy with PSSdiagnosed by high resolution microarray. Initial evaluation was done at age 6 monthsbecause of a history of developmental delay, hypotonia, and dysmorphic face. Coronalcraniosynostosis and enlarged parietal foramina were found on skull radiographs. At age 6yr, he had severe global developmental delay. Multiple exostoses of long bones weredetected during a radiological check-up. Based on the clinical and radiological features,PSS was highly suspected. Subsequently, chromosomal microarray analysis identified an8.6 Mb deletion at 11p11.2 [arr 11p12p11.2 (Chr11:39,204,770-47,791,278) × 1]. Thepatient continued rehabilitation therapy for profound developmental delay. Theprogression of multiple exostosis has being monitored. This case confirms and extends dataon the genetic basis of PSS. In clinical and radiologic aspect, a patient with multipleexostoses accompanying with syndromic features, including craniofacial abnormalities andmental retardation, the diagnosis of PSS should be considered.

신생아 대사이상 선별검사 이상으로 진단된 I형 타이로신혈증

손영배,이해상,이장훈,황진순,Sohn, Young Bae,Lee, Hae-Sang,Lee, Jang Hoon,Hwang, Jin Soon 대한유전성대사질환학회 2012 대한유전성대사질환학회지 Vol.12 No.2

I형 타이로신혈증은 타이로신의 분해 과정 중 최종단계에 관여하는 효소인 fumarylacetoacetate hydrolase(FAH)의 결핍에 의한 대사 이상질환이다. 급성 I형 타이로신혈증은 치명적인 간부전이나 혈액응고장애와 같은 급성 임상증상이 나타난 이후에는 예후가 불량하였으나 최근에는 신생아 대사이상 선별검사를 통해 조기 진단이 가능해졌고 2-(2-nitro-4-trifluoro-methylbenzyol)-1,3 cyclohexanedione nitisinone (NTBC) 약물 치료로 타이로신혈증의 치료 성적이 향상됨에 따라 신생아 대사이사 선별검사를 통한 조기 진단과 조기 치료가 더욱 중요해졌다고 할 수 있다. 이에 저자들은 심각한 출혈이나 간부전과 같은 급성 이상 증상이 나타나기 전 신생아 대사이상 선별검사로 조기 진단 및 조기 중재적 치료로 양호한 경과를 보이고 있는 I형 타이로신혈증 1례를 경험하였기에 문헌 고찰과 함께 보고하는 바이다. Tyrosinemia type I is an autosomal recessive inborn error of tyrosine metabolism that caused a mutation. Clinical symptoms include progressive liver damage with liver failure, coagulopathy, hypophosphataemic rickets, renal tubular dysfunction and a high risk of hepatocellular carcinoma. If left untreated, the affected infants may die from liver failure within the first year of life. PharmacoloIcal therapy with 2-(2-nitro-4-trifluoromethylbenzoyl)-1,3-cyclohexanedione (NTBC) has offered an effective therapeutic option in addition to dietary restriction of tyrosine and phenylalanine. As prognosis of tyrosinemia type I is improving with early diagnosis and early treatments, it meets the criteria for a condition that would benefit from newborn screening. We report a case of tyrosinemia type I diagnosed by newborn screening and successive biochemical analysis of plasma and urine, treated by dietary restriction and NTBC.

뮤코다당증의 장기 치료 효과와 한계점 극복을 위한 노력

손영배,Son, Yeong-Bae 대한유전성대사질환학회 2014 대한유전성대사질환학회지 Vol.14 No.1

Mucopolysaccharidoses (MPSs) are a group of rare inherited metabolic diseases caused by deficiency of lysosomal enzymes. MPSs are clinically heterogeneous and characterized by progressive deterioration in visceral, skeletal and neurological functions. The aim of this article is to review the treatment of MPSs, the unmet needs of current treatments and vision for the future including recent clinical trials. Until recently, supportive care was the only option available for the management of MPSs. Hematopoietic stem cell transplantation (HSCT), another potentially curative treatment, is not routinely advocated in clinical practice due to its high risk profile and lack of evidence for efficacy. From the early 2000s, enzyme replacement therapy (ERT) was approved and available for the treatment of MPS I, II and VI. ERT is effective for the treatment of many somatic symptoms, particularly walking ability and respiratory function, and remains the mainstay of MPS treatment. However, no benefit was found in the neurological symptoms because the enzymes do not readily cross the blood-brain barrier (BBB). In recent years, intrathecal (IT) ERT, substrate reduction therapy (SRT) and gene therapy have been rapidly gaining greater recognition as potential therapeutic avenues. Although still under investigation, IT ERT, SRT and gene therapy are promising MPS treatments that may prevent the neurodegeneration not improved by ERT.

유체역학의 원리 학습을 위한 WBI 프로그램 개발 연구

손영배,박대우,Son, Young-Bae,Park, Dea-Woo 한국정보통신학회 2010 한국정보통신학회논문지 Vol.14 No.10

중 고등학교에서 유체역학의 원리를 학습할 때 실험 실습에 있어서 시공간의 제약으로 학습에 실효성이 떨어지는 문제점이 있다. 본 논문에서는 파스칼의 원리, 아르키메데스의 원리, 베르누이의 정리 등 유체역학에 관한 학습을 웹 브라우저에서 구현하고 Flash와 HTML 등을 이용한 Web 시뮬레이션을 구현하고자 한다. 구현한 WBI(Web Based Instruction) 프로그램은 공업계 고등학교 학생들을 대상으로 만족도, 흥미도, 성취도 측면에서 15%이상의 효과를 나타낸 것으로 비교 분석 되었다. 유체역학의 교육공학적 설계와 웹 설계를 통하여 실제 웹서버를 통하여 인터넷 초고속 통신망에서 구현한다. 본 연구는 교육공학과 유체역학 및 인터넷 원격교육 발전에 기여 할 것이다. In middle and high school to learn the principles of fluid mechanics to Experiments in space and time constraints and difficulties for the study of the principles of fluid mechanics to the problem is superficial. In this paper, Pascal's principles, Archimedes' Principle, Bernoulli's Theorem, etc. learning about the fluid mechanics and implemented in Web Browser, In connection with flash and HTML, web simulation is to implement. Web Based Instruction program that implemented a comparative analysis became an effect of 15% to industrial total high school students in satisfaction, Interest, Achievement. The fluid mechanics education through engineering design and web design through the actual web server is implemented on the Internet over broadband. Department of Education, this study the fluid mechanics and the Internet will contribute to the development of distance education.

Familial Glycogen Storage Disease Type IXa Diagnosed by Targeted Exome Sequencing

손영배,장주영,이다근,장자현,Sohn, Young Bae,Jang, Ju Young,Lee, Dakeun,Jang, Ja-Hyun The Korean Society of Inherited Metabolic Disease 2017 대한유전성대사질환학회지 Vol.17 No.3

당원병 IX형은 phosphorylase kinase 효소 결핍으로 분해되지 않은 당원이 간 또는 근육에 축적되는 유전성대사이상질환이다. 당원병 IXa형은 당원병 IX형 중 가장 흔한 형태로 PHKA2 유전자 변이로 발생한다. 당원병 IXa형의 임상증상은 간 비대, 간 효소 수치 상승, 성장 지연, 저혈당 등이 있다. 그러나, 이러한 임상 증상은 다른 타입의 당원병의 증상과 비슷하거나 겹쳐서 임상적으로는 구분하기가 어렵다. 저자들은 표적 엑솜 시퀀싱으로 진단된 가족성 당원병 IXa형 증례를 보고하고자 한다. 4세 남아가 간 비대와 간 효소 수치 상승을 주소로 내원하였다. 간 조직검사결과 간세포에 당원이 축적되어 있어 당원병을 의심하였으나 G6PC 유전자 검사는 음성이었다. 이에 당원병 타입을 감별진단 하기 위해 표적 엑솜시퀀싱을 시행하였으며, PHKA2 유전자에서 질환과의 연관성이 이미 보고된 바 있는 c.3632C>T (p.Thr121Met) 변이가 반접합체(hemizygote)로 발견되어 당원병 IXa로 진단하였다. 가족 유전자 검사를 통해 어머니가 이형접합체 보인자임을 확인하였으며, 남동생이 같은 변이를 가진 반접합체임을 확인하였다. 28개월 된 환자의 남동생 역시 신체 검진 상 간 비대가 있었으며, 혈액검사상 간 효소 수치가 상승되어 있어 같은 질환으로 확진하였다. 이환된 형제 모두 생 옥수수 전분 섭취와 복합 탄수화물을 섭취하도록 식이 조절을 하였으며 2년 추적관찰 동안 정상 성장 발달을 보이고 있다. 당원병과 같이 임상적으로 구분이 어려우며 유전학적으로 다양한 유전자 변이를 보이는 당원병과 같은 질환의 분자 유전학적 감별진단에 표적 엑솜 시퀀싱이 유용한 진단법이 될 수 있다. 신속하고 정확한 분자 유전학적 감별진단을 통해 환자와 보호자에게 질병의 적절한 치료법, 질병의 예후에 관한 정확한 정보를 제공할 수 있을 뿐 아니라, 적절한 유전상담을 제공할 수 있다. Glycogen storage disease type IX (GSD IX) is caused by deficiency of phosphorylase kinase which plays a role in breakdown of glycogen. Mutations in PHKA2 are the most common cause of GSD IX (GSD IXa). Clinical manifestations of GSD IXa include hepatomegaly, elevation of liver enzyme, growth retardation, fasting hypoglycemia, and fasting ketosis. However, the symptoms overlap with those of other types of GSDs. Here, we report Korean familial cases with GSD IXa whose diagnosis was confirmed by targeted exome sequencing. A 4-year old male patient was presented with hepatomegaly and persistently elevated liver enzyme. Liver biopsy revealed swollen hepatocyte filled with glycogen storage, suggesting GSDs. Targeted exome sequencing was performed for the differential molecular diagnosis of various types of GSDs. A hemizygous mutation in PHKA2 were detected by targeted exome sequencing and confirmed by Sanger sequencing: c.3632C>T (p.Thr121Met), which was previously reported. The familial genetic analysis revealed that his mother was heterozygous carrier of c.3632C>T mutation and his 28-month old brother had hemizygous mutation. His brother also had hepatomegaly and elevated liver enzyme. The hypoglycemia was prevented by frequent meals with complex carbohydrate, as well as cornstarch supplements. Their growth and development is in normal range. We suggest that targeted exome sequencing could be a useful diagnostic tool for the genetically heterogeneous and clinically indistinguishable GSDs. A precise molecular diagnosis of GSD can provide appropriate therapy and genetic counseling for the family.

The metabolic syndrome and body composition in childhood cancer survivors

손영배,김수진,박성원,김세화,Sung-Yoon Cho,이수현,유건희,성기웅,정재훈,구홍회,진동규 대한소아청소년과학회 2011 Clinical and Experimental Pediatrics (CEP) Vol.54 No.6

Purpose: Long-term survivors of childhood cancer appear to have an increased risk for the metabolic syndrome, subsequent type 2diabetes and cardiovascular disease in adulthood compared to healthy children. The purpose of this study was to investigate the frequency of the metabolic syndrome and associated factors in childhood cancer survivors at a single center in Korea. Methods: We performed a retrospective review of medical records of 98 childhood cancer survivors who were diagnosed and completed anticancer treatment at Samsung Medical Center, Seoul, Korea between Jan. 1996 and Dec. 2007. Parameters of metabolic syndrome were evaluated between Jan. 2008 and Dec. 2009. Clinical and biochemical findings including body fat percentage were analyzed. Results: A total of 19 (19.4%) patients had the metabolic syndrome. The median body fat percentage was 31.5%. The body mass index and waist circumference were positively correlated with the cranial irradiation dose (r=0.38, P<0.001 and r=0.44, P<0.00, respectively). Sixty-one (62.2%) patients had at least one abnormal lipid value. The triglyceride showed significant positive correlation with the body fat percentage (r=0.26, P=0.03). The high density lipoprotein cholesterol showed significant negative correlation with the percent body fat (r=-0.26, P=0.03). Conclusion: Childhood cancer survivors should have thorough metabolic evaluation including measurement of body fat percentage even if they are not obese. A better understanding of the determinants of the metabolic syndrome during adolescence might provide preventive interventions for improving health outcomes in adulthood.