Background: The excessive storage of cellular debris in the lysosomal storage disorders triggers a variety of cellular responses. Some of these responses are maladaptative and result in the pathology of these diseases. To some extent, cellular responses are specific to the stored material, which influences the pathophysiology of the disease and results in some of its characteristic features. Methods: A large body of data has been collected for three biochemical (surrogate) markers of Gaucher Disease: angiotensin converting enzyme (ACE), tartrate-resistant acid phosphatase (TRAP) and chitotriosidase (CHITO) using currently available enzyme analysis. Follow up data was gathered in a group of 18 patients. Results: The three markers are correlated between each other and are useful indicators of the disease progress and its response to enzyme replacement therapy (ERT). Retrospective analysis of clinical records and comparison of chitotriosidase values with the baseline Severity Score Index (SSI) allowed prediction of the response patterns for this marker when long-term ERT (>24 months) was evaluated. Conclusions: The less severely affected patients are more likely to normalize their chitotriosidase activities after long term ERT.