Hyaluronan Metabolism, Defect In

Clinical Features

Ramsden et al. (2000) reported a boy with generalized folding and thickening of the skin, which had been recognized by sonogram prenatally and had been striking since birth. During the newborn period, the child displayed persistent mild tachycardia (50 to 60 breaths per minute) but no other abnormal cardiorespiratory signs. Skin biopsy showed a normal epidermis but marked thickening of the dermis, with collagen fibers appearing to be pushed apart by a basophilic granular material that showed positive staining with Alcian blue and anomalous staining with Giemsa stain; this material was confirmed to be hyaluronan. Muscle biopsy revealed no significant abnormality. Ramsden et al. (2000) found that the patient's skin contained gross accumulation of hyaluronan, and the serum concentration of hyaluronan was markedly elevated (up to 3100 mug/L) during infancy. Hyaluronan synthase activity of cultured dermal fibroblasts was increased, whereas hyaluronidase activity in plasma was normal. The patient's skin underwent marked changes after the neonatal period. The face and scalp showed the earliest and most striking changes, with a marked reduction in skin thickness, erythema, and folding. Subsequently, well-demarcated and symmetrically distributed zones of thinning developed over the thighs and back. In each area, thinning was heralded by loss of erythema. Although folding decreased over much of the patient's body, the skin of the anterior chest and abdomen, which had been thickened but flat at birth, became deeply folded in the first months of life and remained so thereafter. Those areas of skin that were normal in appearance at later stages had an unusual, velvety texture. Injury to the skin by blunt trauma, abrasion, or surgical incision was associated with local recurrence of marked thickening and erythema that persisted for several months. Folding of these new areas, however, did not occur. Application of topical corticosteroids appeared to hasten wound healing and diminish local recurrence of hyaluronan accumulation. Ramsden et al. (2000) stated that this disorder is clinically distinct from mucopolysaccharidosis type IX (601492), which also features hyaluronidase deficiency.

In a patient with hyaluronidase deficiency reported by Natowicz et al. (1996), plasma hyaluronidase was undetectable and plasma hyaluronan concentrations were markedly elevated late in childhood. Furthermore, this patient had short stature, periarticular soft tissue masses, and acetabular erosions, all features not present in the patient reported by Ramsden et al. (2000).

Animal Model

Prompted by the similarity between the clinical findings in their patient and the dermatologic findings in the Chinese shar-pei dog, Ramsden et al. (2000) demonstrated that plasma hyaluronan concentrations were higher in shar-pei dogs than in control dogs.