FAILURE OF SHORT-TERM MANNOSE THERAPY OF PATIENTS WITH CARBOHYDRATE-DEFICIENT GLYCOPROTEIN SYNDROME TYPE 1A

Carbohydrate-deficient glycoprotein syndrome type 1A (CDGS1A) is an in herited disorder with multi-systemic abnormalities resulting from fail ure to generate sufficient lipid-linked oligosaccharide precursor or t o transfer the sugar chain to many glycoproteins. Cultured fibroblasts from these patients have reduced incorporation of mannose into glycop roteins which can be corrected by adding D-mannose to the culture medi um. Providing dietary mannose to elevate mannose concentrations in viv o therefore might remedy some of the underglycosylation in the patient s. Five children with CDGS1A aged 15 months to 14 y completed a protoc ol of enteral supplementation with D-mannose 100 mg/kg every 3 h for 9 d. The mean S-mannose level increased from 32 mu M (range 22-42 mu M) to a trough value of 72 mu M (range 39-103 mu M). NO serious side eff ects were observed. Surprisingly, the mean serum concentration of four glycoproteins (transferrin, alpha 1-antitrypsin, antithrombin, and th yroxine-binding globulin) tended to decrease, and the mean serum conce ntration of carbohydrate-deficient transferrin (CDT) increased. Furthe rmore, the initially present abnormal isoforms of these glycoproteins and of protein C became more prominent and/or additional abnormal isof orms appeared. This short-term trial does not support a benefit of man nose to the deficient glycosylation of CDGS1A patients.