Chitotriosidase genotype and plasma activity in patients type 1 Gaucher's disease and their relatives (carriers and non carriers).

BACKGROUND AND OBJECTIVES Chitinases are enzymes that hydolyze chitin and have been found in a wide variety of nonvertebrate species; recently an human analogue of chitinases, chitotriosidase (CT) has been identified. Extreme elevations of plasma CT activity are observed in patients with Gaucher disease (GD), being Gaucher cells the source of the CT. It has been reported a 24 bp duplication in CT gene that results an inactive protein. The carrier prevalence is high as 30 to 40% and the CT activity is half that in wild individuals. However no systematic evaluation of plasma CT activity has been carried in GD patients taken into account status of allele defective for CT and dose in patients on enzyme replacement therapy (ERT). DESIGN AND METHODS We had previously study 210 subjects from 99 unrelated Spanish GD families; 121 were non-affected carriers and 89 were non-carriers to establish carrier prevalence of CT genotypes. Plasma CTactivity and CTgenotypes by PCR and gel electrophoresis have been measured in 109 GD patients before treatment. We also evalued CT activity after ERT with alglucerase in 68 patients. RESULTS Three patients had defective activities of CT. The carrier prevalence for 24 bp duplication was 35% and the allele frequency 0.20. No correlation between CT activity and GBA genotype was detected and between CT activity and visceral or skeletal disease in GD patients. Untreated affected patients, non-carriers for the duplication, had higher CT activity than carriers (p<.0001). CT activity decreased dramatically during the first 12 months of ERT; even after 3 years of therapy a persistent fall of CT activity was observed. How ever within 3 years of treatment, a significant difference in the mean decrease of CT activity was present among the groups of patients on varying alglucerase doses (p<.01). After 12 months of ERT the activity of plasma CT decline in the same percentage in both groups: heterozygous for the carriers of 24bp duplication and wild type, but thereafter CT activity decline more slowly in carriers than non carriers. INTERPRETATION AND CONCLUSIONS The present data can be used as a reference to interpret the CT activity in GD patients with or without ERT, as well as to evaluate the doses response and can be used as a reference to interpret the CTactivity in carriers and non-carriers.