BACKGROUND Complex polysaccharides, glycosaminoglycans (GAGs), their amount, and fine structure were determined in the skin (epidermis + dermis) of pseudoxanthoma elasticum (PXE)-affected patients in comparison with healthy subjects. METHODS Nonlesional skin GAGs were extracted and specifically determined by enzymatic treatment and high-performance liquid chromatography separation. RESULTS Dermatan sulfate (DS) and hyaluronic acid (HA) were found to be the major GAG species in normal subjects, with contents of approximately 20% for DS and 58% for HA. The chondroitin sulfate (CS) content (unsaturated six-sulfated disaccharide) was approximately 21%. Skin from patients with PXE showed similar HA (61%), DS (22%), and CS (16.7%) contents. No change in the total charge density or nonsulfated/sulfated GAG ratio was noted in PXE-affected subjects, and no modification of the position of the sulfate groups (4s/6s) on the CS/DS backbone. A significant increase (approximately 88%; P < 0.01) in the total amount of GAGs (HA + DS + CS) was found in the PXE group vs. normal subjects, however. CONCLUSIONS In the skin of PXE-affected patients, the altered metabolic processes produce an increase in the total amount of GAGs able to accumulate salts, in particular calcium ions, within the elastic fibers, producing ion precipitates that affect the organization of the matrix fiber.