ORAL INGESTION OF MANNOSE ELEVATES BLOOD MANNOSE LEVELS - A FIRST STEP TOWARD A POTENTIAL THERAPY FOR CARBOHYDRATE-DEFICIENT GLYCOPROTEIN SYNDROME TYPE-I

Carbohydrate-deficient glycoprotein syndrome type I (CDGS) is an inher ited metabolic disorder with multisystemic abnormalities resulting fro m a failure to add entire N-linked oligosaccharide chains to many glyc oproteins. Fibroblasts hom these patients also abnormally glycosylate proteins, but this lesion is corrected by providing 250 mu M mannose t o the culture medium. This correction of protein glycosylation suggest s that providing dietary mannose to elevate blood mannose concentratio ns might also remedy some of the underglycosylation observed in these patients. We find that ingested mannose is efficiently absorbed and in creases blood mannose levels in both normal subjects and CDGS patients . Blood mannose levels increased in a dose-dependent fashion with incr easing oral doses of mannose (0.07-0.21 g mannose/kg body weight). Pea k blood mannose concentrations occurred at 1-2 h following ingestion a nd the clearance half-time was approximately 4 h. Doses of 0.1 g manno se/kg body weight given at 3-h intervals maintained blood mannose conc entrations at levels 3- to 5-fold higher than the basal level in both normal controls (similar to 55 mu M) and CDGS patients. No side effect s were observed for this dosage regimen. These results establish the f easibility of using mannose as a potential therapeutic dietary supplem ent (nutraceutical) to treat CDGS patients. (C) 1996 Academic Press.