Serum hyaluronidase aberrations in metabolic and morphogenetic disorders

Abstract

Hyaluronidases are endo-glycosidases that degrade both hyaluronan (hyaluronic acid) (HA) and chondroitin sulfates. Deficiency of hyaluronidase activity has been predicted to result in a phenotype similar to that observed in mucopolysaccharidosis (MPS). In the present study, we surveyed a variety of patients with phenotypes similar to those observed in MPS, but without significant mucopolysacchariduria to determine if some are based on aberrations in serum hyaluronidase (Hyal-1) activity. The study included patients with well-characterized dysmorphic disorders occurring on genetic basis, as well as those of unkown etiology. The purpose of the study was to establish how wide spread were abnormalities in levels of circulating Hyal-1 activity. A simple and sensitive semi-quantitative zymographic procedure was used for the determination of activity. Levels of both beta-N-acetylglucosaminidase and beta-glucuronidase whose activities contribute to the total breakdown of hyaluronan (HA) were also measured, as well as the concentration of circulating HA. Among 48 patients with bone or connective tissue abnormalities, low levels of Hyal-1 activity were found in six patients compared to levels in 100 healthy donors (2.0-3.2 units/microL vs 6(+/- 1 SE) units/microL). These six patients exhibited a wide spectrum of clinical abnormalities, in particular shortened extremities: they included three patients with unknown causes of clinical symptoms, one patient with Sanfilippo disease, one of the seven patients with achondroplasia, and one with hypophosphotemic rickets. Normal levels of serum Hyal-1 activities were found in patients with Morquio disease, GM1 gangliosidosis, I cell-disease, 6 of the 7 patients with achondroplasia, Marfan's-syndrome and Ehlers-Danlos syndrome. No patient totally lacked serum Hyal-1 activity. Serum HA concentration was elevated in patients with Sanfilippo A and I-cell disease. Determination of serum and leukocyte Hyal-1 and serum HA may be useful to evaluate patients with metabolic and morphogenetic disorders.

Screening Mucopolysaccharidosis Type IX in Patients with Juvenile Idiopathic Arthritis

“…and some without any specific diagnosis (osteoporosis, dysplasia, skeleton deformities, etc.) were tested for hyaluronidase enzyme levels, and deficient enzyme activity was not detected in these patients, either (Fiszer-Szafarz et al 2005). Serum Hyal-1 activity was also enhanced in this survey, which was consistent with previous studies.…”

Hyaluronan as an Immune Regulator in Human Diseases

“…Patients with advanced scleroderma have decreased serum HYAL-1 activity and elevated circulating levels of HA (297). In one study, six patients with bone or connective tissue abnormalities had lower levels of HYAL-1 activity than did healthy donors (100). Reactive oxygen species accumulate at sites of tissue injury and may provide a mechanism for generating HA fragments in vivo.…”

JIMD Reports, Volume 25

“…Deficient hyaluronidase enzyme activity was not detected in any of these patients (Goldberg et al 1991;Paimela et al 1991;Nagaya et al 1999). were tested for hyaluronidase enzyme levels, and deficient enzyme activity was not detected in these patients, either (Fiszer-Szafarz et al 2005). In another study of 48 patients with bone or connective tissue abnormalities, some with specific diagnosis (mucopolysaccharidoses, Ehlers-Danlos syndrome, achondroplasia, osteogenesis imperfecta, etc.)…”