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Value of plasma chitotriosidase to assess non‐neuronopathic Gaucher disease severity and progression in the era of enzyme replacement therapy
Author(s) -
Dussen L.,
Hendriks E. J.,
Groener J. E. M.,
Boot R. G.,
Hollak C. E. M.,
Aerts J. M. F. G.
Publication year - 2014
Publication title -
journal of inherited metabolic disease
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.462
H-Index - 102
eISSN - 1573-2665
pISSN - 0141-8955
DOI - 10.1007/s10545-014-9711-x
Subject(s) - enzyme replacement therapy , substrate reduction therapy , glucocerebrosidase , medicine , bone marrow , enzyme , gastroenterology , plasma cell , spleen , disease , endocrinology , multiple myeloma , chemistry , biochemistry
Gaucher disease (GD) is caused by deficiency of the enzyme glucocerebrosidase catalysing the regular lysosomal degradation of glucosylceramide. In the common non‐neuropathic variant of GD, glucosylceramide‐laden macrophages (Gaucher cells) accumulate in various tissues. Gaucher cells secrete chitotriosidase, an active chitinase, resulting in increased plasma chitotriosidase levels, which can be sensitively monitored by an enzyme activity assay. Plasma chitotriosidase is a rough estimate of body burden of Gaucher cells. Non‐neuronopathic GD is presently treated by enzyme replacement therapy (ERT) and substrate reduction therapy (SRT). We addressed the question whether plasma chitotriosidase acts as (predictive) marker of clinical manifestations in non‐neuronopathic GD patients receiving treatment. Reductions in plasma chitotriosidase during therapy correlated with corrections in liver and spleen volumes and showed positive trends with improvements in haemoglobin and platelet count and bone marrow composition. The occurrence of long‐term complications and associated conditions such as multiple myeloma, bone complications, Parkinson's disease, hepatocellular carcinoma and pulmonary hypertension positively correlated with the plasma chitotriosidase level pre‐therapy, the average plasma chitotriosidase during 3 years of ERT and the residual plasma chitotriosidase after 2 years of ERT. In summary, plasma chitotriosidase is a valuable marker in the assessment and follow‐up of GD patients.