Value of plasma chitotriosidase to assess non-neuronopathic Gaucher disease severity and progression in the era of enzyme replacement therapy

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 chitotr...

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Bibliographic Details
Published in:Journal of inherited metabolic disease 2014-11, Vol.37 (6), p.991-1001
Main Authors: van Dussen, L., Hendriks, E. J., Groener, J. E. M., Boot, R. G., Hollak, C. E. M., Aerts, J. M. F. G.
Format: Article
Language:English
Subjects:
Adolescent
Adult
Aged
Aged, 80 and over
Biochemistry
Biological and medical sciences
Biomarkers - blood
Child
Disease Progression
Enzyme Replacement Therapy - methods
Errors of metabolism
Female
Follow-Up Studies
Gaucher Disease - drug therapy
Glucosylceramidase - therapeutic use
Glucosylceramides - metabolism
Hexosaminidases - blood
Human Genetics
Humans
Internal Medicine
Lipids (lysosomal enzyme disorders, storage diseases)
Liver - metabolism
Macrophages - metabolism
Male
Medical genetics
Medical sciences
Medicine
Medicine & Public Health
Metabolic Diseases
Middle Aged
Original Article
Pediatrics
Retrospective Studies
Spleen - metabolism
Treatment Outcome
Young Adult
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Summary: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.
ISSN:0141-8955
1573-2665
DOI:10.1007/s10545-014-9711-x