875 ZINC THERAPY IN MANNOSIDOSIS

Abstract

Our previous observation that ZnSO4, added in vitro, both stimulated and stabilized residual leukocyte acidic α-mannosidase activity in two patients (Arch. Neurol. 34, 45, 1977) prompted a therapeutic trial of the metal. Oral ZnSO4 in doses ranging from 13-45 mg/kg over a 12-week period raised serum Zn levels to a maximum of twice normal. Average leukocyte acid α-mannosidase activity during the treatment period ranged from 2-5% of control values, showing no significant difference from baseline levels. No treatment related change occurred in the 11 band thin layer chromatographic profile of mannose containing neutral oligosaccharides excreted in a 24-hour urine. Because Zn is known to have a high affinity for tissue uptake, 1 ml containing 10 mg ZnSO4 was injected into the gingiva of patient 1, which had become hyperplastic with PAS-positive storage material. A control site was injected with an equal volume of saline. Biopsies before and one month after the injections showed no change in the ultrastructural characteristics of membrane bound cytoplasmic vacuoles. The Zn injected tissue had a moderately increased amount of collagenous stroma, which was not seen in either the saline or pre-injection controls. This may reflect a positive effect on wound healing. Otherwise, ZnSO4 does not appear to have specific therapeutic efficacy in ameliorating storage material in mannosidosis under the above conditions.