MUCOPOLYSACCHARIDE ACCUMULATION IN CULTURED SKIN FIBROBLASTS DERIVED FROM PATIENTS WITH MUCOLIPIDOSIS-IV

Abstract

Increased concentrations of total sulfated mucopolysaccharides (MPS), 3-fold, and hyaluronic acid (HA), 10-fold, were found in human skin ML [mucolipidosis] IV fibroblast extracts when compared to normal controls. Such accumulations altered distribution of MPS: HA comprised 70% of total MPS in ML IV but only 30% in control cells. Intracellular sulfated MPS was observed accumulating almost linearly in ML IV fibroblasts. Pulse-chase experiments indicate that both HA and the sulfated MPS remain in the ML IV cells for long periods of time; in control cells, they are rapidly removed as low MW, dialyzable fragments. The MPS accumulation in ML IV fibroblasts may be the consequence of a catabolic block, probably involving the lysosome.