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

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.

Niveis sericos de hormonio de crescimento na sindrome de Hunter / Serum growth hormone levels in Hunter's syndrome

Os niveis sericos de hormonio de crescimento (GH) foram estudados em tres irmaos com sindrome de Hunter (Mucopolissacaridose tipo II). A dinamica da secrecao do GH foi analisada por meio de testes com insulina (0,05 UI/Kg, i.v.), glicose (1,75 g/Kg, v.o.), lisina vasopressina (LPV) (5 ou 10 UI, i.m.) e L-Dopa (500 mg, v.o.). Os niveis basais de GH durante os quatro testes eram elevados (X = 14,2 ng/ml) nos tres casos. As respostas do GH ao estimulo com insulina e LPV mostraram tendencia a apresentar uma correlacao direta com a idade dos casos analisados, sendo maiores no paciente mais velho. Ao contrario dos dois outros casos, no teste com L-Dopa o paciente mais velho nao mostrou elevacao de niveis de GH. Apos administracao de glicose, os niveis de GH se deprimiram, como esperado nos tres casos. Como valores basais de cortisol e prolactina eram usualmente normais durante estes testes, nao se valorizou a hipotese de que o stress fosse o unico causador dos valores basais elevados de GH. Para tentar melhor esclarecer estes achados, dosaram-se os niveis de GH sob condicoes basais de 20-20 min., durante 120 min.; nos tres casos as medias destes valores de GH eram normais nos casos 1 e 3, enquanto tendiam a se elevar no caso 2. Valores da somatomedina-C eram normais-baixos nos tres casos...