Abstract
Summary: A partial deficiency of α-mannosidase was found in cultured skin fibroblasts, serum, and extracts of leukocytes in two siblings with mild mental retardation, delayed speech, a suggestion of coarse or full facies, and limited mobility of the large joints. All other lysosomal enzymes tested were within the normal range. Their father demonstrated intermediate α-mannosidase activity. The addition of 2 mM Zn++ caused a 40% increase of the α-mannosidase activity in cell extracts of both patients and control subjects. pH profiles and Cellogel electrophoresis of the patients' cells indicated 20% residual activity of the acidic α-mannosidase isoenzyme (pH optimum at 4.0), whereas the activity of the isozyme with pH optimum of 6.0 was normal. Increasing substrate concentration (1–10 mM) demonstrated a 4to 5-fold increase in the apparent Km of the acidic α-mannosidase in the patients' fibroblasts. This residual activity, however, was apparently not sufficient for the normal catabolism of mannose-containing molecules, since electron microscopic examination of the cultured fibroblasts demonstrated numerous lysosomal storage bodies.
Speculation: This family supports the concept that mannosidosis is not a homogeneous syndrome but manifests clinical as well as biochemical heterogeneity. The partial activity of acidic α-mannosidase observed in the cultured fibroblasts (approximately 20%) was insufficient for normal catabolism and allows accumulation of α-mannoside-containing substrates leading to the abnormal pheno-type. Nevertheless, this deduction is based on in vitro studies using a synthetic substrate. The observation that Zn++ causes a 40% stimulation of acidic α-mannosidase activity in the patients' cells agrees with previous findings and may be of significance in the treatment of such cases.
Similar content being viewed by others
Article PDF
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Bach, G., Kohn, G., Lasch, E. et al. A New Variant of Mannosidosis with Increased Residual Enzymatic Activity and Mild Clinical Manifestation. Pediatr Res 12, 1010–1015 (1978). https://doi.org/10.1203/00006450-197810000-00012
Issue Date:
DOI: https://doi.org/10.1203/00006450-197810000-00012
Keywords
This article is cited by
-
Natural history of alpha mannosidosis a longitudinal study
Orphanet Journal of Rare Diseases (2013)
-
Alpha-mannosidosis
Orphanet Journal of Rare Diseases (2008)