A new disorder of hyaluronan metabolism associated with generalized folding and thickening of the skin.
OBJECTIVE
To describe and characterize a new disorder of hyaluronan metabolism associated with marked abnormalities of cutaneous tissue and to determine 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 thickening and folding were examined by light and electron microscopy. The concentration of hyaluronan and the activity of hyaluronidase were measured in the patient's serum and plasma, respectively, and the activity of hyaluronan synthase was examined in cultured dermal fibroblasts. Hyaluronan concentration 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 microg/L) during infancy. Hyaluronan synthase activity of cultured dermal fibroblasts 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 microg/L vs 73 microg/L, respectively).


CONCLUSIONS
The child we describe has a novel disorder of hyaluronan metabolism, which appears to result from abnormal control of hyaluronan synthesis. An analogous disorder may be present in the shar-pei dog.
Ramsden
C A
CA
Department of Newborn Services, Monash Medical Centre, Clayton, Victoria, Australia.
Bankier
A
A
Brown
T J
TJ
Cowen
P S
PS
Frost
G I
GI
McCallum
D D
DD
Studdert
V P
VP
Fraser
J R
JR
D000818:Animals; D001706:Biopsy; D002478:Cells, Cultured; D004285:Dogs; D005347:Fibroblasts / Q000201:enzymology; D005500:Follow-Up Studies; D014453:Glucuronosyltransferase / Q000378:metabolism; D016695:Glycosyltransferases; D006801:Humans; D000076002:Hyaluronan Synthases; D006820:Hyaluronic Acid / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D006821:Hyaluronoglucosaminidase / Q000097:blood; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008565:Membrane Proteins; D008854:Microscopy, Electron; D010641:Phenotype; D012867:Skin / Q000378:metabolism* / Q000473:pathology; D012871:Skin Diseases / Q000209:etiology* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D014166:Transferases; D029867:Xenopus Proteins
D008565:Membrane Proteins; D029867:Xenopus Proteins; D006820:Hyaluronic Acid; D014166:Transferases; D016695:Glycosyltransferases; D014453:Glucuronosyltransferase; C056944:HAS1 protein, Xenopus; D000076002:Hyaluronan Synthases; D006821:Hyaluronoglucosaminidase