Oral ingestion of mannose elevates blood mannose levels: a first step toward a potential therapy for carbohydrate-deficient glycoprotein syndrome type I

Abstract

Carbohydrate-deficient glycoprotein syndrome type I (CDGS) is an inherited metabolic disorder with multisystemic abnormalities resulting from a failure to add entire N-linked oligosaccharide chains to many glycoproteins. Fibroblasts from these patients also abnormally glycosylate proteins, but this lesion is corrected by providing 250 microM mannose to the culture medium. This correction of protein glycosylation suggests that providing dietary mannose to elevate blood mannose concentrations might also remedy some of the underglycosylation observed in these patients. We find that ingested mannose is efficiently absorbed and increases blood mannose levels in both normal subjects and CDGS patients. Blood mannose levels increased in a dose-dependent fashion with increasing oral doses of mannose (0.07-0.21 g mannose/kg body weight). Peak blood mannose concentrations occurred at 1-2 h following ingestion and the clearance half-time was approximately 4 h. Doses of 0.1 g mannose/ kg body weight given at 3-h intervals maintained blood mannose concentrations at levels 3- to 5-fold higher than the basal level in both normal controls (approximately 55 microM) and CDGS patients. No side effects were observed for this dosage regimen. These results establish the feasibility of using mannose as a potential therapeutic dietary supplement (nutraceutical) to treat CDGS patients.