Clinical and Experimental Pediatrics

The Korean Pediatric Society (대한소아청소년과학회)
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Clinical Findings of Genotypes in Korean Patients with Glycogen Storage Disease Type Ia

한국인 당원병 제 Ia형에서 유전형의 임상 양상

  • Ko, Jae Sung (Department of Pediatrics, Seoul National University College of Medicine) ;
  • Yang, Hye Ran (Department of Pediatrics, Seoul National University College of Medicine) ;
  • Kim, Jong Won (Department of Laboratory Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine) ;
  • Seo, Jeong Kee (Department of Pediatrics, Seoul National University College of Medicine)
  • 고재성 (서울대학교 의과대학 소아과학교실) ;
  • 양혜란 (서울대학교 의과대학 소아과학교실) ;
  • 김종원 (성균관대학교 의과대학 삼성서울병원 진단의학과) ;
  • 서정기 (서울대학교 의과대학 소아과학교실)
  • Received : 2005.03.04
  • Accepted : 2005.04.19
  • Published : 2005.08.15
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Abstract

Purpose : Glycogen storage disease type Ia(GSD Ia) is an autosomal recessive disorder caused by the deficiency of glucose-6-phosphatase(G6Pase). The aim of the study was to investigate the spectrum of G6Pase gene mutations and relationship between genotype and clinical findings in Korean patients with GSD Ia. Methods : Genomic DNA was extracted from peripheral leukocytes of 20 patients with GSD Ia. The five exons of G6Pase gene were amplified and PCR products were directly sequenced. The frequency of short stature, hypoglycemia, hypercholesterolemia, hyperuricemia, hypercalciuria, nephrocalcinosis and hepatic adenoma was compared between 727G>T homozygotes and 727G>T compound heterozygotes. Results : A total of 5 different mutations were identified. The most common mutation was the 727G>T with an allele frequency of 80%. All patients were either homozygous(12/20) or heterozygous(8/20) for the 727G>T mutation. G122D was found in 3 patients, P178A in 1, G222R in 2, and S339R in 2. There was no difference in the frequency of short stature, hypoglycemia, hypercholesterolemia, hyperuricemia, nephrocalcinosis, and hepatic adenoma between 727G>T homozygotes and heterozygotes. Conclusion : Diagnosis of GSD Ia can be based on clinical and biochemical abnormalities combined with mutation analysis instead of enzymatic diagnosis that requires liver biopsy. Homozygosity for the 727G>T does not seem to alter the disease phenotype as compared with the heterozygous state.

목 적 : 한국인 당원병 제 Ia형 환자에서 G6Pase 유전자 돌연변이를 찾아내고, 유전형과 임상양상과의 연관관계를 밝히는 것이다. 방 법 : 서울대학교병원 소아과에서 Ia형 당원병으로 진단 받은 환자 20명을 대상으로 G6Pase 유전자에 대하여 직접 염기서열 분석하였다. 유전형과 임상 양상의 상관성을 알아보기 위하여 진단시 연령, 저신장, 저혈당, 고콜레스테롤혈증, 고요산혈증, 고칼슘뇨증, 신석회화증, 간선종 발생을 조사하였다. 결 과 : 총 5종류의 돌연변이가 발견되었고, splice site 돌연변이인 727G>T가 40개의 대립 유전자 중 32개에서 발견되어 80%의 빈도를 보였다. 전체 20명 중에서 12명이 727G>T 동형접합자이고, 8명이 727G>T 복합 이형접합자이었다. 8명의 이형접합자에서 G122D 3명, P178A 1명, G222R 2명, 새로운 돌연변이인 S339R 2명 등 다른 돌연변이를 찾을 수 있었다. 727G>T 동형접합자와 복합 이형접합자 두 군 사이에 저신장, 저혈당, 고콜레스테롤혈증, 고요산혈증, 신석회화증, 간선종의 빈도는 차이를 보이지 않았다. 결 론 : 임상 양상, 생화학적 검사와 함께 유전자 돌연변이 분석을 이용하면 간생검을 통한 효소측정을 하지 않고 Ia형 당원병을 진단할 수 있으며, 727G>T 동형접합 돌연변이가 이형접합과 비교할 때 질병 양상에 큰 영향을 미치지 않는다.

Keywords

Acknowledgement

Supported by : 서울대학교병원

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