title: Changes in glycogen and glycosaminoglycan levels in hepatocytes of iduronate-2-sulfatase knockout mice before and after recombinant iduronate-2-sulfatase supplementation.
abstract: OBJECTIVE
  Mucopolysaccharidosis II (MPS II) is a lysosomal storage disorder caused by a deficiency of iduronate-2 sulfatase (IdS), which is involved in the degradation of glycosaminoglycan (GAG). In this study, the frequency of fasting hypoglycemia in patients with MPS II was investigated and changes in accumulation of glycogen and GAG in the hepatocytes of IdS-knockout (KO) mice were evaluated before and after recombinant IdS enzyme replacement therapy (ERT).
  
  
  METHODS
  Plasma glucose levels were evaluated after an 8-hour fast in 50 patients with MPS II. The IdS-KO mice were divided into three groups (group 2; saline, group 3; 0.15 mg/kg of IdS, and group 4; 0.5 mg/kg of IdS); wild-type mice were included as controls (group 1). ERT was initiated intravenously at four weeks of age, and continued every week until 20 weeks of age.
  
  
  RESULTS
  The mean glucose level after an 8-hour fast was 94.1 ± 23.7 mg/dL in the patients with MPS II. Two (4%) out of 50 patients had fasting hypoglycemia. For the mice, GAG in the lysosomes nearly disappeared and glycogen particles in the cytoplasm were restored to the normal range in group 4.
  
  
  CONCLUSIONS
  Glucose metabolism in patients with MPS II appeared to function well despite hepatocytic GAG accumulation and hypothetical glycogen depletion. A higher dose of IdS infusion in MPS II mice led to disappearance of lysosomal GAG and restoration of glycogen to the cytoplasm of hepatocytes.
authors.affiliation: Department of Pediatrics, Kangnam Sacred Heart Hospital, Hallym University School of Medicine, Seoul, Korea.
authors.forename: Jee Hyun
authors.initials: JH
authors.lastname: Lee
authors.forename: Yon Ho
authors.initials: YH
authors.lastname: Choe
authors.forename: Su Jin
authors.initials: SJ
authors.lastname: Kim
authors.forename: Kyung Hoon
authors.initials: KH
authors.lastname: Paik
authors.forename: Dong-Kyu
authors.initials: DK
authors.lastname: Jin
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D056947:Enzyme Replacement Therapy / Q000379:methods; D006003:Glycogen / Q000032:analysis*; D006025:Glycosaminoglycans / Q000032:analysis*; D022781:Hepatocytes / Q000737:chemistry / Q000201:enzymology*; D006801:Humans; D007003:Hypoglycemia / Q000201:enzymology / Q000503:physiopathology; D007066:Iduronate Sulfatase / Q000235:genetics / Q000502:physiology*; D008099:Liver / Q000648:ultrastructure; D051379:Mice; D018345:Mice, Knockout; D008854:Microscopy, Electron; D016532:Mucopolysaccharidosis II / Q000097:blood / Q000201:enzymology / Q000503:physiopathology
chemical_list: D001786:Blood Glucose; D006025:Glycosaminoglycans; D006003:Glycogen; D007066:Iduronate Sulfatase