ENZYME MANIPULATION: EVALUATION OF ORAL ZnSO4 SUP-PLEMENTATION IN MANNOSIDOSIS TYPE II

Abstract

Mannosidosis types I and II (M I/II) have been differentiated by phenotypic (Pediat.Res. 10:985,1976) and now by enzymatic characterization. M I/II variants both showed residual acidic (pH 4.4) α-mannosidase (αM) activity (1-3% of normal (N)), which was cryolablle; intriguingly, decreased neutral (pH 6.0) αM was consistently found in WBC (<25% of N) but not in fibroblasts or plasma. Thermal inactivation (55°C, pH 4.4 and pH 6.0) revealed differential αM stabilities in M I/II fibroblasts; different Km values were found only at pH 4.4. Zn++ and Co++ stimulated the residual αM in M I/II plasma and WBC. ZnSO4 (0.3mM) incubated in the media of cultured M I/II fibroblasts stimulated residual αM > 200% of untreated controls after 2d. These in vitro studies suggested that oral ZnSO4 supplementation may increase substrate catabolism in vivo. Four sibs of consanguineous parents with M II participated in a 6 mo controlled (2 treated; 2 untreated) study. The αM activities were unchanged in plasma, WBC and tears in either group. Urinary mannose-rich oligosaccharides appeared to decrease in treated patients. These results indicate 1) genetic heterogeneity of M, 2) a molecular interrelationship among the isozymes, 3) enzyme manipulation by Zn++ in vitro, and finally 4) Zn++ supplementation in M II may stimulate residual tissue αM and increase substrate catabolism.