Yonsei Med J.  2011 Mar;52(2):263-267. 10.3349/ymj.2011.52.2.263.

Changes in Glycogen and Glycosaminoglycan Levels in Hepatocytes of Iduronate-2-Sulfatase Knockout Mice before and after Recombinant Iduronate-2-Sulfatase Supplementation

• Lee JH
• Choe YH
• Kim SJ
• Paik KH
• Jin DK

• KMID: 1779661
• DOI: http://doi.org/10.3349/ymj.2011.52.2.263

Abstract

PURPOSE
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).
MATERIALS AND 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.
CONCLUSION
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.

Keyword

Mucopolysaccharidosis II; iduronate-2-sulfatase knockout mice; glycogen; glycosaminoglycan; idursulfase supplementation; liver histology

MeSH Terms

Animals
Blood Glucose/analysis
Enzyme Replacement Therapy/methods
Glycogen/*analysis
Glycosaminoglycans/*analysis
Hepatocytes/chemistry/*enzymology
Humans
Hypoglycemia/enzymology/physiopathology
Iduronate Sulfatase/genetics/*physiology
Liver/ultrastructure
Mice
Mice, Knockout
Microscopy, Electron
Mucopolysaccharidosis II/blood/enzymology/physiopathology

Figure

• 

  Fig. 1 High power electron microscopic findings (9.0 × 9,000). (A) Wild type: the arrow shows large amounts of glycogen particles in the cytoplasm. (B) MPS II model: the arrow shows accumulation of GAG in lysosomes and scanty glycogen content in the cytoplasm. (C) Low dose ERT group: GAG in the lysosomes decreases but restoration of glycogen in the cytoplasm is not remarkable. (D) High dose ERT group: GAG in the lysosomes nearly disappears and glycogen particles in the cytoplasm are restored. MPS II, mucopolysaccharidosis II; GAG, glycosaminoglycan; ERT, enzyme replacement therapy.

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