Effect of time of initiating enzyme replacement therapy on immune dysfunction in patients with Gaucher disease

Abstract

CO RR EC TE D P RO OF a test (Filipin test) performed in living fibroblasts obtained from a skin biopsy, with the positive and inconclusive results usually having to be further investigated by molecular analysis of the NPC1 and NPC2 genes (30 exons in total). Assays for other lysosomal enzymes may also be performed along the investigation, as needed. Chitotriosidase (CT) activity is increased in most NPC patients, but this test is not very specific as high activities are also observed in Gaucher, Niemann–Pick types A/B, acid lipase deficiency and several other conditions. The analysis of oxysterols has recently been proposed as a potential method to identify NPC patients, especially cholestan-3β,5α,6β-triol (triol). Our group coordinates a large network of Brazilian services which investigates patients at risk of presenting NPC. Samples from high-risk patients investigated by the measurement of CT activity (plasma) and by the Filipin test (cultured fibroblasts), were also submitted to the tandem mass spectrometry assay of triol (plasma). In 21 high-risk patients investigated we found that all 3 cases with positive Filipin test had also increased triol levels (with CT also increased). In 9 patients in whom Filipin test resulted inconclusive, 1 had increased triol levels, with CT activity also increased, being potentially a variant NPC case (enzyme assays ruled out another LSD, and molecular analysis for NPC1 and NPC2 is in progress). In 9 cases with negative Filipin test, triol was normal in all except one, who had also increased CT levels and was later diagnosed with Niemann–Pick disease type A. These preliminary results, which should be expanded and completed with the results of the molecular analysis of the NPC1 and NPC2 genes, suggest that oxysterol measurement, although not specific, is a noninvasive, fast and sensitive method that could play a role in the screening of NPC disease.