Journal of The Korean Society of Inherited Metabolic disease (대한유전성대사질환학회지)

The Korea Society of Inherited Metabolic Disease (대한유전성대사질환학회)
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AGL gene mutation and clinical features in Korean patients with glycogen storage disease type III

한국인 제3형 당원병 환자의 임상상 및 AGL 유전자형

  • Ko, Jung Min (Dept. of Pediatrics, University of Ulsan College of Medicine) ;
  • Lee, Jung Hyun (Dept. of Pediatrics, University of Ulsan College of Medicine) ;
  • Kim, Gu-Hwan (Medical Genetics Clinic and Lab, University of Ulsan College of Medicine) ;
  • Yoo, Han-Wook (Dept. of Pediatrics, University of Ulsan College of Medicine)
  • 고정민 (울산대학교 의과대학 소아과학교실) ;
  • 이정현 (울산대학교 의과대학 소아과학교실) ;
  • 김구환 (서울 아산병원 의학유전학 클리닉) ;
  • 유한욱 (울산대학교 의과대학 소아과학교실)
  • Published : 2006.07.15
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Abstract

Purpose: Glycogen storage disease type III (GSD-III), is a rare autosomal recessive disorder of glycogen metabolism. The affected enzyme is amylo-1,6-glucosidase, 4-alpha-glucanotransferase (AGL, glycogen debranching enzyme), which is responsible for the debranching of the glycogen molecule during catabolism. The disease has been demonstrated to show clinical and biochemical heterogeneity, reflecting the genotype-phenotype heterogeneity among different patients. In this study, we analyzed mutations of the AGL gene in three unrelated Korean GSD-III patients and discussed their clinical and laboratory implications. Methods: We studied three GSD-III patients and the clinical features were characterized. Sequence analysis of 35exons and part exon-intron boundaries of the AGLgene in patients were carried out by direct DNA sequencing method using genomic DNA isolated from patients' peripheral leukocytes. Results: The clinical features included hepatomegaly (in all patients), seizures (in patient 2), growth failure (in patients 1), hyperlipidemia (in patients 1 and 3), raised transaminases and creatinine kinase concentrations (in all patients) and mild EKG abnormalities (in patients 2). Liver transplantation was performed in patient 2due to progressive hepatic fibrosis. Administration of raw-corn-starch could maintain normoglycemia and improve the condition. DNA sequence analysis revealed mutations in 5 out of 6 alleles. Patient 1 was a compound heterozygote of c.1282 G>A (p.R428K) and c.1306delA (p.S603PfsX6), patient 2 with c.1510_1511insT (p.Y504LfsX10), and patient 3 with c.3416 T>C (p.L1139P) and c.l735+1 G>T (Y538_R578delfsX4) mutations. Except R428K mutation, 4 other mutations identified in3 patients were novel. Conclusion: GSD-III patients have variable phenotypic characteristics resembling GSD-Ia. The molecular defects in the AGL gene of Korean GSD-III patients were genetically heterogeneous.

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