RESUMO
Mucolipidosis types II and III are autosomal recessive inherited diseases caused by a deficiency in the lysosomal enzyme N-acetylglucosamine-1 phosphotransferase (GlcNAc-phosphotransferase), which adds phosphate to function as a recognition marker for the uptake and transport of lysosomal enzymes. We investigated mutations in the GNPTA (MGC4170) gene, which codes for the alpha/beta subunits of phosphotransferase, and in the GNPTAG gene, which codes for its gamma subunits in five Korean patients with mucolipidosis type II or IIIA. We identified seven mutations in the GNPTA gene, but none in GNPTAG. The mutations in type II patients included p.Q104X (c.310C>T), p.R1189X (c.3565C>T), p.S1058X (c.3173C>G), p.W894X (c.2681G>A), and p.H1158fsX15 (c.3474_3475delTA), all of which are nonsense or frameshift mutations. However, a splicing site mutation, IVS13+1G>A (c.2715+1G>A) was detected along with a nonsense or a frameshift mutation (p.R1189X or p.E858fsX3 (c.2574_2575delGA)) in two mucolipidosis type IIIA patients. This report shows that mutations in the GNPTA gene coding for the alpha/beta subunits of phosphotransferase, and not mutations in the GNPTAG gene, account for most of the genetic mutations found in Korean patients with mucolipidosis type II or IIIA.
Assuntos
Povo Asiático/genética , Mucolipidoses/genética , Mutação , Transferases (Outros Grupos de Fosfato Substituídos)/genética , Adolescente , Adulto , Criança , Pré-Escolar , Análise Mutacional de DNA , Feminino , Testes Genéticos , Humanos , Lactente , Recém-Nascido , Masculino , Mucolipidoses/metabolismo , Transferases (Outros Grupos de Fosfato Substituídos)/metabolismoRESUMO
The plasma ghrelin has been reported to be elevated in Prader-Willi syndrome (PWS) and modulated by insulin. It was hypothesized that insulin might have a more pronounced effect on reducing plasma ghrelin in PWS patients, which would influence appetite. This study investigated the degree of ghrelin suppression using an euglycemic hyperinsulinemic clamp in children with PWS (n=6) and normal children (n=6). After a 90-min infusion of insulin, the plasma ghrelin level decreased from a basal value of 0.86+/-0.15 to 0.58+/-0.12 ng/mL in the controls, and from 2.38+/-0.76 to 1.12+/-0.29 ng/mL in children with PWS (p=0.011). The area under the curve below the baseline level over the 90 min insulin infusion was larger in children with PWS than in controls (-92.82+/-44.4 vs. -10.41+/-2.87 ng/mL/90 min) (p=0.011). The insulin sensitivity measured as the glucose infusion rate at steady state was similar in the two groups (p=0.088). The decrease in the ghrelin levels in response to insulin was more pronounced in the children with PWS than in the controls. However, the level of ghrelin was always higher in the children with PWS during the clamp study. This suggests that even though insulin sensitivity to ghrelin is well maintained, an increase in the baseline ghrelin levels is characteristic of PWS.