A new disorder of hyaluronan metabolism associated with generalized folding and thickening of the skin

Objective: To describe and characterize a new disorder of of hyaluronan met abolism associated with marked abnormalities of cutaneous tissue and to det ermine whether a relationship with a phenotypically similar disorder in the shar-pei dog exists. Methods: Biopsy specimens of the skin of a child with extreme cutaneous thi ckening and folding were examined by light and electron microscopy. The con centration of hyaluronan and the activity of hyaluronidase were measured in the patient's serum and plasma, respectively and the activity of hyalurona n synthase nas examined in cultured dermal fibroblasts. Hyaluronan concentr ation was also measured in the plasma of 23 shar-pei and 34 control dogs. Results: The patient's skin displayed gross accumulation of hyaluronan, and the serum concentration of hyaluronan was markedly elevated (up to 3100 mu g/L) during infancy. Hyaluronan synthase activity of cultured dermal fibro blasts was increased, whereas hyaluronidase activity in plasma was normal ( 5.5 +/- 0.08 IU/L). Plasma hyaluronan concentration was higher in the shar- pei dogs than in control dogs (median, 378 mu g/L vs 73 mu g/L, respectivel y). Conclusion: The child we describe has a novel disorder of hyaluronan metabo lism, which appears to result from abnormal control of hyaluronan synthesis . An analogous disorder may be present in the shar-pei dog. (J Pediatr 2000 ;136:62-8).