Gaucher disease: comparative study of acid phosphatase and glucocerebrosidase in normal and type-1 Gaucher tissues.

ABSTRACT

Acid phosphatase activity was determined in serum, cultured fibroblasts, and peripheral blood lymphocytes of six splenectomized adult patients with non-neuropathic Gaucher disease in two Canadian families. Elevated levels of serum acid phosphatase activity (520-711% of normal) were found in four patients who also developed orthopedic complications associated with Gaucher disease, including intermittent bone pain, arthritis, collapse of femoral head, and pathological fractures. Serum acid phosphatase activity in two patients who do not have bone involvement were found to be within the normal range. Contrary to the serum enzyme, acid phosphatase activity in lymphocytes and cultured fibroblasts of all of the patients was within the normal range. Deficient glucocerebrosidase (7.5-15.5% of normal) and acid beta-glucosidase (13.8-27.8% of normal) activities were noted in all probands. Similarly, normal levels of fibroblast and lymphocyte acid phosphatase activity were found in Gaucher heterozygotes whose glucocerebrosidase activity was about 50% of normal. Acid polyacrylamide gel electrophoresis and acid phosphatase activity staining of the patients' sera showed that the elevated acid phosphatase is isozyme type 5 osteoclastic origin. The apparent Michaelis constant, Km, of fibroblast glucocerebrosidase for the natural substrate was 0.6 +/- 0.1 mM for controls and 0.6 +/- 0.2 mM for the patients. These data suggest that the assay of serum acid phosphatase activity for the presumptive diagnosis of Gaucher disease is not completely reliable and that the elevated level of serum acid phosphatase in Gaucher disease is most likely a secondary phenomenon which may be indicative of bone involvement in some patients with this disorder. It also demonstrates the clinical heterogeneity of type 1 Gaucher disease, even among full sibs of the same heterozygous parents.