• Journal of Genetic Medicine
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• 제5권1호
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• pp.21-25
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• 2008

목 적 : 최근 여러 국가에서 빠르게 탠덤매스 신생아 선천성 대사이상질환 선별 프로그램을 채택하고 있으며 많은 질환들이 검출되고 있다. 본 기관에서는 2001년 4월부터 탠덤 매스 선천성 대사이상 질환 신생아 선별 검사를 시작하였다. 연구자들은 한국에서의 탠덤매스 선천성 대사이상질환 검출율 및 탠덤매스 유용성에 대해 평가하고자 하였다. 방 법 : 2001년 4월부터 2007년 12월까지 본원에서는 탠덤매스를 이용하여 신생아 및 고위험군에 대해 선별검사를 시행하였다. 검체로부터 아실카르틴과 아미노산을 추출하여 부탄올로 유도체화시킨 후 탠덤매스에 장착하여 분석하였다. 탠덤매스 선별검사 재검, 소변 유기산 및 혈장 아미노산 검사 등을 포함한 확진 검사는 개별적으로 시행되었다. 결 과 : 총 의뢰건수는 284,933건으로 신생아 251,799건 및 고위험군 33,134건이었다. 소환율은 0.4%(1158건)이었으며, 이들 중 true positive는 117건(0.04%)이었다. 아미노산 대사 이상 질환은 총 78건(25/53), 유기산 대사이상 질환은 총 27건(16/11건) 및 지방산 산화대사이상 질환은 총 12건(5/7건)으로 전체 질환에 대한 검출율은 신생아 1:5,000이었으며 전체군 1:2,000이었다. 결 론 : 탠덤매스 신생아 선별검사는 조기 진단 및 치료가 필요한 많은 선천성 대사이상질환의 검출을 용이하게 해주었다. 그러므로, 반드시 모든 신생아들에 대한 국가지원 탠덤매스 선별검사 확대 적용 및 추적관리 시스템이 구축이 필요할 것으로 판단된다.

• 대한유전성대사질환학회지
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• 제6권1호
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• pp.58-62
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• 2006

Gaucher disease is an inherited disorder due to a deficiency in the activity of glucocerebrosidase (EC. 3.2.1.45) by genetic mutation which resulted from missense, nonsense, frameshift, deletion in long arm 21 of chromosome 1 (1q21). Gaucher disease is classified into the main three types as type 1 (nonneuronopathic), type 2 (acute neuronopathic) and type 3 (subacute neuronopathic) according to the progressive phase of manifestations and nervous system involvement. Gaucher disease patients had been treated by using the method as splenectomy and bone marrow transplantation. But enzyme replacement therapy as a more effective treatment has been available since the early 1990's. In order to treat Gaucher disease efficiently by using ERT, it is necessary to chase the progress of the therapy. In this study, therefore, we tried to chase the progress of the ERT by using the measurement of chitotriosidase activity in Gaucher disease patients.

• 대한유전성대사질환학회지
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• 제18권2호
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• pp.50-54
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• 2018

Jehovah's Witnesses do not accept blood transfusions, because of their particular interpretation of the Old and New Testaments. When people with such religious convictions are in need of medical care, their faith and belief may become an obstacle for proper treatment, and pose legal, ethical, and medical challenges for the health care providers. We report two inherited metabolic disorder cases in South Korea where the infants died whilst under medical care because of parental refusal of blood transfusions for religious reasons. Case 1 had methylmalonic acidemia, Down syndrome and associated congenital cardiac anomalies requiring surgery. Case 2 had anemia and methylmalonic acidemia requiring dialysis to treat hyperammonemia and metabolic acidosis. For effective medical management, they needed life-saving blood transfusions. As a part of alternative treatment, Erythropoietin was administered in both cases. As a result, two babies died from their extremely low hemoglobin and hematocrit. The hemoglobin concentrations below 2.7 g/dL without cardiac problem and 5.4 g/dL with cardiac anomaly complicated by pulmonary hypertension are considered life-threatening hemoglobin threshold. The medical professional must respect and accommodate religious beliefs of the patients who can make informed decisions. However, when parents or legal guardians oppose medical treatment of their babies and incompetent care receivers on cultural and religious grounds, the duty to assist and save persons exposed to serious danger, particularly life-threatening events must come first.

• 대한유전성대사질환학회지
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• 제5권1호
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• pp.18-22
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• 2005

저자들은 Pompe 병으로 진단된 3세 남아에 recombinant human GAA 정주를 통한 효소 보충 치료를 시행하여 운동 능력과 심기능이 호전되며 간비대도 호전된 1례를 경험하였기에 보고하는 바이다.

• 대한유전성대사질환학회지
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• 제5권1호
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• pp.9-17
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• 2005

Homocystinuria is a metabolic disorder caused by a deficiency of cystathionine ${\beta}$-synthase (CBS). Patients with homocystinuria show clinical symptoms such as mental retardation, lens dislocation, vascular disease with life-threatening thromboembolisms and skeletal deformities. Generally, the major treatments for CBS deficiency include pharmacologic doses of pyridoxine or dietary restriction of methionine. However, there is no effective treatment for this disease up till today and gene therapy can be an attractive novel approach to treatment of the disease. We investigated whether a recombinant adeno-associated virus could be used as a CBS gene transfer vector to reduce the excessive homocysteine level in the homocystinuria mouse model. Recombinant adeno-associated virus vector encoding the human CBS gene (rAAV-hCBS), driven by EF1-a promoter, was infused into CBS-deficient mice ($CBS^{-/-}$) via intramuscular (IM) and intraperitoneal (IP) injection. IP injection was more efficient than IM injection for prolongation of lives and reduction of plasma homocysteine levels. After 2 weeks of gene transfer by IP injection, serum homocysteine level was significantly decreased in treated mice compared with the age-matched controls and the life span was extended about 1.5 times. Also, increased expression of CBS gene was observed by immunohistochemical staining in livers of treated $CBS^{-/-}$ mice and microvesicular lipid droplets was decreased in cytoplasm of liver. These results demonstrate the possibility and efficacy of gene therapy by AAV gene transfer in homocystinuria mice.

• 대한유전성대사질환학회지
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• 제16권2호
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• pp.57-61
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• 2016

IVA는 상염색체 열성의 유전방식을 보이는 leucine 대사 장애 질환이자 대표적인 유기산 혈증이다. IVD 유전자의 돌연변이에 의한 isovaleryl-CoA dehydrogenase 효소의 결핍이 질환 발생의 원인이다. Isovaleryl-CoA dehydrogenase 효소가 결핍되면 isovaleryl-CoA의 대사물질이 비정상적으로 체내에 축적되어 대사성 산증 및 고암모니아혈증 등의 급성 대사성 위기와 발달지연, 성장지연, 및 경련성질환 등의 만성 합병증을 초래할 수 있기 때문에, 급성 대사성 위기 및 만성합병증의 발생을 예방하기 위해 조기 진단에 따른 적절한 치료의 도입이 중요하다. 현재 IVA은 국내에서 시행되는 탠덤 매스 스크리닝법을 이용한 신생아 대사질환 선별검사 항목에 포함되어 있으며, C5의 상승으로 의심할 수 있다. 그러나 SBCAD 결핍증 혹은 pivalic acid 유래물이 포함된 항생제를 투여한 경우에도 C5의 상승이 동반될 수 있기 때문에, 감별진단 및 확진을 위한 추가적인 생화학적, 유전학적 검사가 필수적이다.

• Journal of Genetic Medicine
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• 제19권2호
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• pp.94-99
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• 2022

Lesch-Nyhan disease (LND) is a rare X-linked recessive inherited purine metabolic disorder that accompanies neurodevelopmental problems. Neurofibromatosis type 1 (NF1) is a relatively common autosomal dominant inherited genetic disorder characterized by tumors in various systems. Some children with NF1 also accompanies neurodevelopmental problems. Here, we describe a 5-year-old boy with a maternally inherited pathogenic variant in NF1 and hypoxanthine-guanine phosphoribosyltransferase (HPRT). He was referred for severe neurodevelopmental impairment and hyperuricemia. His mother was diagnosed with NF1 and the patient was also suspected of having NF1 because of cafe au lait macules. He had dystonia, rigidity, cognitive deficit, and speech/language impairment. Serum and urine uric acid concentrations were elevated. He had more severe neurodevelopmental delay than patients with only NF1, so his clinical symptoms could not be fully understood by the disease alone. To find the cause of his neurologic symptoms and hyperuricemia, the patient and his mother underwent a whole-exome sequencing test. As a result, the pathogenic variant c.151C>T (p.Arg51Ter) in HPRT1 was identified as hemizygote in the patient and heterozygote in his mother. The pathogenic variant c.7682C>G (p.Ser2561Ter) in NF-1 was identified as heterozygotes in both of them. Although the clinical symptoms of both diseases were overlapping and complicated, genetic testing was helpful for accurate diagnosis and treatment. Therefore, we suggest to consider preemptive genetic evaluation if there are symptoms not sufficiently explained by known existing diseases. And it is considered valuable to review this rare case to understand the clinical course and possible synergic effects of these diseases.

• 대한유전성대사질환학회지
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• 제6권1호
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• pp.32-39
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• 2006

저자들은 출생 후 정상적인 발달을 보이다가 생후 6개월부터 의식과 운동 발달의 퇴행을 보이던 13개월 환아에서 효소 검사를 시행하여 ${\beta}$-galactosidase의 결핍을 확인하고 $GM_1$-gangliosidosis type 1으로 진단하였지만, 후에 추가적으로 시행한 효소 검사에서 ${\alpha}$-neuraminidase의 결핍도 발견되어 galactosialidosis로 진단한 증례를 경험하였기에 문헌 고찰과 함께 보고하고자 한다.

• 대한유전성대사질환학회지
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• 제15권3호
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• pp.160-164
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• 2015

Hunter syndrome(Mucopolysaccharidosis type II, MPS type II) is an X-linked disorder of glycosaminoglycans (GAGs) metabolism caused by an iduronate-2-sulfatase (IDS2) deficiency. A 24-month-old boy visited the department of pediatrics with the chief compliant of chronic purulent rhinorrhea beginning at age one. He had a history of repeated acute otitis media and chronic rhinitis. On physical examination he had a coarse face, enlarged tongue, distended abdomen, joint stiffness, and Mongolian spots at his first visit. The urine GAGs level was elevated at 66.10 mg/mmolCr (reference range, <11.1) and iduronate-2-sulfatase activity in leukocyte was decreased at 0.21 nmol/mg protein/hr (reference range, 18.7-57). Finally with an IDS gene mutational analysis, recombinant known mutation between intron 7 and distal of exon 3 in IDS2 was detected. Recombinant iduronate-2-sulfatase therapy was started without any infusion related reactions. The author highlights the importance of suspecting Hunter syndrome when pediatric patients visit with chronic purulent rhinorrhea which is a common cause of hospital visits for infants and children.

• 대한유전성대사질환학회지
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• 제13권1호
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• pp.30-36
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• 2013

6-pyruvoyltetrahydropterin synthase (PTPS) deficiency is autosomal recessive disorder and the most common type of tetrahydrobiopterin (BH4) deficiency. It is caused by deficiency of PTPS, a cofactor involved in the biosynthesis of BH4 from guanosine triphosphate (GTP). Unlike classical phenylketonuria, which needs restriction of dietary phenylalanine for whole life, BH4 deficiency is treated by tetrahydrobiopterin, levodopa, and 5-hydroxytryptophan replacement. So it is important to make accurate diagnosis and initiate treatment as soon as possible for a better prognosis. There is no retrospective study of Korean patients undergoing long-term treatment for PTPS deficiency. We report 9 Korean patients with PTPS deficiency and their laboratory findings including BH4 loading tests, urine pterin tests, genotypes, dihydropteridine reductase (DHPR) activities and clinical manifestations including medication and developmental delay existence.