Clinical utility of chitotriosidase enzyme activity in nephropathic cystinosis (Orphanet Journal of Rare Diseases)

Background: Nephropathic cystinosis is an inherited autosomal recessive lysosomal storage disorder characterized by the pathological accumulation and crystallization of cystine inside different cell types. WBC cystine determination forms the basis for the diagnosis and therapeutic monitoring with the cystine depleting drug (cysteamine). The chitotriosidase enzyme is a human chitinase, produced by activated macrophages. Its elevation is documented in several lysosomal storage disorders. Although, about 6% of Caucasians have enzyme deficiency due to homozygosity of 24-bp duplication mutation in the chitotriosidase gene, it is currently established as a screening marker and therapeutic monitor for Gaucher?s disease. Methods: Plasma chitotriosidase activity was measured in 45 cystinotic patients, and compared with 87 healthy controls and 54 renal disease patients with different degrees of renal failure (CKD1-5). Chitotriosidase levels were also correlated with WBC cystine in 32 treated patients. Furthermore, we incubated control human macrophages in-vitro with different concentrations of cystine crystals and monitored the response of tumor necrosis factor-alpha (TNF-?) and chitotriosidase activity. We also compared plasma chitotriosidase activity in cystinotic knocked-out (n?=?10) versus wild-type mice (n?=?10). Results: Plasma chitotriosidase activity in cystinotic patients (0?3880, median 163?nmol/ml/h) was significantly elevated compared to healthy controls (0?90, median 18?nmol/ml/h) and to CKD patients (0?321, median 52?nmol/ml/h), P?