MARKED ELEVATION OF PLASMA CHITOTRIOSIDASE ACTIVITY - A NOVEL HALLMARK OF GAUCHER DISEASE

Gaucher disease (GD; glucosylceramidosis) is caused by a deficient act ivity of the enzyme glucocerebrosidase (GC). Clinical manifestations a re highly variable and cannot be predicted accurately on the basis of the properties of mutant GC. Analysis of secondary abnormalities, such as elevated plasma levels of some hydrolases, may help to increase in sight into the complicated pathophysiology of the disease and could al so provide useful disease markers. The recent availability of enzyme s upplementation therapy for GD increases the need for markers as early predictors of the efficacy of treatment. We report the finding of a ve ry marked increase in chitotriosidase activity in plasma of 30 of 32 s ymptomatic type 1 GD patients studied: the median activity being >600 times the median value in plasma of healthy volunteers. In three GC-de ficient individuals without clinical symptoms, only slight increases w ere noted. Chitotriosidase activity was absent in plasma of three cont rol subjects and two patients. During enzyme supplementation therapy, chitotriosidase activity declined dramatically. We conclude that plasm a chitotriosidase levels can serve as a new diagnostic hallmark of GD and should prove to be useful in assessing whether clinical manifestat ions of GD are present and for monitoring the efficacy of therapeutic intervention.