BACKGROUND: Juvenile hyaline fibromatosis (JHF) is a rare autosomal recessive disease characterized histologically by deposition of hyaline material and clinically by multiple skin lesions. Clarification of the molecular and structural changes involved in JHF skin lesions may unravel targets for pharmacotherapy.OBJECTIVE: We sought to investigate the expression of glycosaminoglycans and their metabolizing enzymes in lesional as compared with lesion-free skin tissue specimens in JHF.METHODS: Glycosaminoglycans were isolated, purified, and fractionated by electrophoresis on cellulose acetate membranes and agarose gels. Hyaluronic acid (HA) was quantitated by enzyme-linked immunosorbent assay and the expression of HA metabolizing enzymes was investigated using reverse transcriptase-polypeptide chain reaction.RESULTS: JHF lesions exhibited significantly less HA and elevated amounts of dermatan sulfate and chondroitin sulfate, whereas gene expression of HA synthase-1 and HA synthase-3 was significantly down-regulated, as compared with lesion-free skin tissue specimens.LIMITATIONS: Because JHF is a rare disease, a limitation to our study was that we collected skin tissue specimens from only one patient.CONCLUSION: The significant alterations of HA homeostasis in JHF lesions provide further understanding of JHF pathogenesis and may offer a target for pharmacologic intervention to treat the skin lesions associated with JHF.