Impact of Enzyme Replacement Therapy on Linear Growth in Korean Patients with Mucopolysaccharidosis Type II (Hunter Syndrome)

조성윤,허림,장미선,이지은,Younghee Kwun,Se-Hyun Maeng,김수진,손영배,박성원,권은경,Sun Ju Han,정주연,진동규 대한의학회 2014 Journal of Korean medical science Vol.29 No.2

Hunter syndrome (or mucopolysaccharidosis type II [MPS II]) arises because of a deficiency in the lysosomal enzyme iduronate-2-sulfatase. Short stature is a prominent and consistent feature in MPS II. Enzyme replacement therapy (ERT) with idursulfase (Elaprase®) or idursulfase beta (Hunterase®) have been developed for these patients. The effect of ERT on the growth of Korean patients with Hunter syndrome was evaluated at a single center. This study comprised 32 patients, who had received ERT for at least 2 yr; they were divided into three groups according to their ages at the start of ERT: group 1 (<6 yr, n=14), group 2 (6-10 yr, n=11), and group 3 (10-20 yr, n=7). The patients showed marked growth retardation as they got older. ERT may have less effect on the growth of patients with the severe form of Hunter syndrome. The height z-scores in groups 2 and 3 revealed a significant change (the estimated slopes before and after the treatment were -0.047 and -0.007, respectively: difference in the slope, 0.04; P<0.001). Growth in response to ERT could be an important treatment outcome or an endpoint for future studies.

2.5세에 진단된 헌터증후군 1례

최미란,권영희,진동규,이지은,Choi, Miran,Kwun, Younghee,Jin, Dongkyu,Lee, Jieun 대한유전성대사질환학회 2014 대한유전성대사질환학회지 Vol.14 No.2

Hunter syndrome (mucopolysaccharidosis type II, MPS II) is a X-linked lysosomal storage disease caused by a deficiency in the lysosomal enzyme, iduronate-2-sulfatase (IDS), leading to accumulation of glycosaminoglycans within lysosomes of many organs and tissues. Since the enzyme replacement therapy was approved and available in the treatment of MPS I, II, VI, early diagnosis and early therapy can bring the better prognosis of disease and the better quality of life in patients. We described a 2.5 year old child presented with frequent otitis media and developmental delay including speech impairment, who was diagnosed as Hunter syndrome with IDS NM_000202.5:c. 263G>A(p.Arg88His) mutation.

ABCD1 유전자 c.1252C>T의 돌연변이가 확인된 X-연관성 대뇌부신백질형성장애 1례

김유선,허림,권영희,이지은,조성윤,기창석,진동규,Jeong, Yu Ju,Huh, Rimm,Kwun, Younghee,Lee, Jieun,Cho, Sung Yoon,Ki, Chang-Seok,Jin, Dong-Kyu 대한유전성대사질환학회 2014 대한유전성대사질환학회지 Vol.14 No.1

부신백질형성장애는 성염색체-연관성 유전대사 질환으로 ABCD1 유전자의 돌연변이에 의해 발생한다. 이중 대뇌 부신백질형성장애는 부신백질형성장애의 한 표현형으로, 급격한 뇌백질의 탈수초화와 부신 기능 부전을 보인다. 9세 남아가 인지 및 신경 기능의 퇴행을 주소로 내원하여 시행한 혈청 내 매우 긴 사슬 지방산이 증가되어 있었고 뇌 MRI에서 특징적인 양쪽 두정-후두엽 백질의 대칭적 고신호강도 소견을 보였으며 ABCD1 유전자에 돌연변이 c. 1252C>T (p.Arg418 Trp)가 발견되어 이를 보고하는 바이다.

DHCR 7 유전자 돌연변이로 확진된 스미스-렘리-오피츠 증후군 1례

정유주,허림,권영희,이지은,조성윤,기창석,진동규,Jeong, Yu Ju,Huh, Rimm,Kwun, Younghee,Lee, Jieun,Cho, Sung Yoon,Ki, Chang-Seok,Jin, Dong-Kyu 대한유전성대사질환학회 2014 대한유전성대사질환학회지 Vol.14 No.1

Smith-Lemli-Opitz syndrome (SLOS) is an autosomal recessive disease caused by a defect in cholesterol biosynthesis. This mutation encodes 7-dehydrocholesterol reductase (DHCR7), which is located on chromosome 11q13. It is characterized by typical facial appearances, microcephaly, small up-turned nose, cleft palate, syndactyly, and is correlated with cardiac, gastrointestinal and genital malformations. There may also be mental retardation, behavioral problems and growth retardation. It causes a broad spectrum of effects, ranging from a mild disorder of learning and behavior to a lethal malformation. There are four reports of Smith-Lemli-Opitz syndrome in Korean children. Here, we describe a two months old female with microcephaly, toe syndactyly and a cleft soft palate who was diagnosed as SLOS with c. 1054 C>T (p.R352W) and c.907G>A (p. G303R) mutations.

ASS 1 유전자 돌연변이로 확진된 시트룰린혈증 1형 1례

임대균,허림,권영희,이지은,조성윤,박형두,진동규,Yim, Dae kyoon,Huh, Rimm,Kwun, Younghee,Lee, Jieun,Cho, Sung Yoon,Park, Hyung Doo,Jin, Dong-Kyu 대한유전성대사질환학회 2015 대한유전성대사질환학회지 Vol.15 No.1

Citrullinemia type1 is an autosomal recessive disorder of the urea cycle characterized by neonatal or late onset of hyperammonemia caused by a deficiency of the enzyme argininosuccinate synthetase (ASS). An ASS1 deficiency demonstrates fatal clinical manifestations that are characterized by the neonatal metabolic coma and early death when untreated. It causes a broad spectrum of effects, ranging from a mild disorder to a severe mental retardation, epilepsy, neurologic deficits. An acute neonatal form is the most common. Infants are normal at birth followed by an acute illness characterized by vomiting, lethargy, seizures and coma. These medical problems are life-threatening in many cases. A later onset form is less frequent and may be milder than the neonatal form. This later-onset form is associated with severe headaches, visual dysfunction, motor dysfunction, and lack of energy. Citrullinemia type1 is caused by mutations in the ASS1 gene located on chromosome 9q34.1 that encodes argininosuccinate synthetase, the third enzyme of the urea cycle catalyzing the formation of argininosuccinic acid from citrulline and aspartic acid. The enzyme is distributed in tissues including liver and fibroblasts. This mutation leads to hyperammonemia, arginine deficiency and elevated citrulline level. In the urea cycle, argininosuccinate synthetase catalyses the conversion of citrulline and aspartate to argininosuccinate.. Here, we describe a female newborn patient with lethargy, rigidity and hyperammonemia who was diagnosed as citrullinemia type1 with a c.[421-2A>G], c.[1128-6_1188dup] mutation.

무증상 신생아에서 진단된 중쇄 acyl-CoA 탈수소효소 결핍증 1례

경예찬,허림,권영희,이지은,조성윤,진동규,이정호,이동환,Kyung, Yechan,Huh, Rimm,Kwun, Younghee,Lee, Jieun,Cho, Sung Yoon,Jin, Dong-Kyu,Lee, Jeongho,Lee, Dong Hwan 대한유전성대사질환학회 2015 대한유전성대사질환학회지 Vol.15 No.1

Medium-chain acyl-CoA dehydrogenase (MCAD) deficiency is the most common mitochondrial fatty acid oxidation disorder which is inherited as an autosomal recessive pattern. MCAD deficiency is caused by mutations in the ACADM gene; medium-chain acyl-CoA dehydrogenase gene (ACADM; OMIM 607008) on chromosome 1p31 which encodes MCAD, the mitochondrial enzyme which catalyzes the first reaction in beta-oxidation of fatty acids with medium-chain length. Here, we describe one Korean pediatric case of MCAD deficiency, which was diagnosed during newborn screening by tandem mass spectrometry and confirmed by molecular analysis. The level of hexanoyl (C6), octanoyl (C8), decenoyl (C10:1) carnitine, and C8/C2 ratio was elevated. Homogenous c.1189T>A (p.Tyr397Asn) mutation of ACADM gene was identified by direct sequencing. He has been asymptomatic and has shown normal growth and development by 25 months of age without any intervention. There was no episode of metabolic acidosis during follow-up period.

사립체 근병증 환자에서 발생한 자가항체 양성의 당뇨병성 케톤산증 1례

남순영,허림,권영희,이지은,조성윤,진동규,Nam, Soon Young,Huh, Rimm,Kwun, Younghee,Lee, Jieun,Cho, Sung Yoon,Jin, Dong-Kyu 대한유전성대사질환학회 2014 대한유전성대사질환학회지 Vol.14 No.2

Mitochondrial myopathy results from a primary dysfunction of the respiratory chain and is frequently accompanied with endocrine manifestations. Among the endocrine manifestations of mitochondrial disease, diabetes mellitus is relatively common. Diabetes mellitus in the mitochondrial myopathy is usually insulin dependent due to the defect in insulin secretion resulted from mitochondrial dysfunction. But it is seldom manifested as diabetes ketoacidosis and doesn't usually have an auto-antibody. We report a patient with mitochondrial myopathy who was diagnosed as having diabetes mellitus by presenting as diabetes ketoacidosis and had both of the auto-glutamic acid decarboxylase (GAD) antibody and anti-insulin auto-antibody.

임상적으로 진단된 다발성 골단이형성증 1례

김선자,조성윤,김진섭,허림,권영희,이지은,심종섭,김옥화,진동규,Kim, Sun-Ja,Cho, Sung Yoon,Kim, Jinsup,Huh, Rimm,Kwun, Younghee,Lee, Jieun,Shim, Jongsup,Kim, Ok-Hwa,Jin, Dong-Kyu 대한유전성대사질환학회 2015 대한유전성대사질환학회지 Vol.15 No.1

Multiple epiphyseal dysplasia (MED) is one of the more common skeletal dysplasias. MED is characterized by joint pain and stiffness, a waddling gait, and/or mild short stature in childhood. Radiographic findings include delayed and irregular ossification of the epiphyses in multiple joints. Mutations in at least six different genes (COMP, MATN3, COL9A1, COL9A2, COL9A3, and DTDST) can cause MED, and it can be either dominant or recessive inheritance. Molecular diagnosis is important for accurate prognosis and genetic counselling. COMP mutation is the most common form of MED in Western. But, MATN3 mutation was reported as the most common type of MED in Korea. Here, we describe a boy who was diagnosed as MED by clinical and radiological features. Hip radiograph of the patient was suggested MATN3 mutation. But knee radiograph was suggested COMP mutation. MATN3 and COMP mutations direct sequencing, but were no mutation. So we tested whole exome sequencing, but significant variant was not detected as known MED six genes mutations. The patient was diagnosed as having MED clinically and radiologically. Further study to identify the other responsible genes for MED is needed.

Birth seasonality in Korean Prader-Willi syndrome with chromosome 15 microdeletion

Aram Yang,Yeon Hee Lee,Soon Young Nam,Yu Ju Jeong,Ye-Chan Kyung,Rimm Huh,Jieun Lee,Younghee Kwun,Sung-Yoon Cho,진동규 대한소아내분비학회 2015 Annals of Pediatirc Endocrinology & Metabolism Vol.20 No.1

Purpose: Prader-Willi syndrome (PWS) is a well-known genetic disorder, and microdeletion on chromosome 15 is the most common causal mechanism. Several previous studies have suggested that various environmental factors might be related to the pathogenesis of microdeletion in PWS. In this study, we investigated birth seasonality in Korean PWS. Methods: A total of 211 PWS patients born from 1980 to 2014 were diagnosed by methylation polymerase chain reaction at Samsung Medical Center. Of the 211 patients, 138 were born from 2000–2013. Among them, the 74 patients of a deletion group and the 22 patients of a maternal uniparental disomy (UPD) group were compared with general populations born from 2000 using the Walter and Elwood method and cosinor analysis. Results: There was no statistical significance in seasonal variation in births of the total 211 patients with PWS (χ2=7.2522, P=0.2982). However, a significant difference was found in the monthly variation between PWS with the deletion group and the at-risk general population (P<0.05). In the cosinor model, the peak month of birth for PWS patients in the deletion group was January, while the nadir occurred in July, with statistical significance (amplitude=0.23, phase=1.2, low point=7.2). The UPD group showed the peak birth month in spring; however, this result was not statistically significant (χ2=3.39, P=0.1836). Conclusion: Correlation with birth seasonality was identified in a deletion group of Korean PWS patients. Further studies are required to identify the mechanism related to seasonal effects of environmental factors on microdeletion on chromosome 15.

A biochemical and physicochemical comparison of two recombinant enzymes used for enzyme replacement therapies of hunter syndrome

Chung, Yo Kyung,Sohn, Young Bae,Sohn, Jong Mun,Lee, Jieun,Chang, Mi Sun,Kwun, Younghee,Kim, Chi Hwa,Lee, Jin Young,Yook, Yeon Joo,Ko, Ah-Ra,Jin, Dong-Kyu Springer-Verlag 2014 GLYCOCONJUGATE JOURNAL Vol.31 No.4