Decrease of plasma taurine in Gaucher disease and its sustained correction during enzyme replacement therapy.

Abstract

Gaucher disease is caused by an autosomal-recessive deficiency of glucocerebrosidase. Cells of monocytic/macrophagic origin accumulate glucosylceramide. This leads to hepatosplenomegaly, bone destruction, thrombocytopenia and anemia. Enzyme replacement therapy (ERT) with macrophage-targeted glucocerebrosidase leads to normalization of these parameters. The way of macrophage activation in Gaucher disease is not known. Recently, the osmolytes taurine, betaine and inositol were identified as important regulators of macrophage function in liver. Therefore, the role of plasma taurine in Gaucher disease as a primarily macrophage-derived disease was studied. Fasting plasma levels were measured from blood samples of healthy control subjects (n = 29, m:f = 11:18, mean age 37 +/- 3 years), from untreated Gaucher patients (n = 16, m:f = 7:9, mean age 44 +/- 4 years) and those treated for 37 +/- 2 months (n = 54, m:f = 19:35, mean age 47 +/- 2 years). Amino acid analysis was carried out in a BioChrom amino acid analyzer. In the untreated patients, plasma taurine was 45 +/- 3 microM, as compared to the controls with a plasma taurine of 63 +/- 4 microM (p < 0.01). The average increase of plasma taurine during the first year of ERT was 18 +/- 8 microM (n = 10). Patients treated for an average of 37 months (range 1-9 years of ERT) had a plasma taurine of 65 +/- 4 microM (n = 54), which was not different from the controls. It is concluded that Gaucher patients show decreased plasma taurine levels and that therapy of Gaucher disease might correct this. It has to be established, whether decreased taurine availability is a cofactor of the permanent activation of glucosylceramide-storing monocytes/macrophages in this disease.