Alteration of mannose transport in fibroblasts from type I carbohydrate deficient glycoprotein syndrome patients

The aim of the present study was to explore how mannose enters fibroblasts derived from a panel of children suffering from different subtypes of type I carbohydrate deficient glycoprotein syndrome: seven carbohydrate deficien t glycoprotein syndrome subtype Ia (phosphomannomutase deficiency), two car bohydrate deficient glycoprotein syndrome subtype Ib (phosphomannose isomer ase deficiency) and two carbohydrate deficient glycoprotein syndrome subtyp e Ix (not identified deficiency). We showed that a specific mannose transpo rt system exists in all the cells tested but has different characteristics with respect to carbohydrate deficient glycoprotein syndrome subtypes, Subt ype Ia fibroblasts presented a mannose uptake equivalent or higher (maximum 1.6-fold) than control cells with a D-[2-H-3]-mannose incorporation in nas cent N-glycoproteins decreased up to 7-fold. Compared to control cells, the mannose uptake was greatly stimulated in subtype Ib (4.0-fold), due to low er K-uptake and higher V-max values. Subtype Ib cells showed an increased i ncorporation of D-[2-H-3]mannose into nascent N-glycoproteins, Subtype Ix f ibroblasts presented an intermediary status with mannose uptake equivalent to the control but with an increased incorporation of D-[2-H-3]-mannose in nascent N-glycoproteins. All together, our results demonstrate quantitative and/or qualitative modifications in mannose transport of all carbohydrate deficient glycoprotein syndrome fibroblasts in comparison to control cells, with a relative homogeneity within a considered subtype of carbohydrate de ficient glycoprotein syndrome. These results are consistent with the possib le use of mannose as a therapeutic agent in carbohydrate deficient glycopro tein syndrome Ib and Ix. (C) 1999 Elsevier Science B.V. All rights reserved .