Chitotriosidase on treatment-naïve patients with Gaucher disease: A genotype vs phenotype study

Background: Chitotriosidase (ChT) is used as a biomarker for the follow-up of patients with Gaucher disease (GD), once his activity is extremely elevated and declines during ERT. However, some variants in the CHIT1 gene affect ChT activity.

Methods: To assess association between ChT genotype, and clinical/biochemical features of GD were performed CHIT1 genotyping for: c.1049_1072dup24, p.Gly102Ser, p.Gly354Arg, c.1155_1156 + 2delGAGT, c.1156 + 5_1156 + 8delGTAA, p.Ala442Val/Gly and the rearrangement delE/I-10.

Results: Were evaluated 42 patients with GD from Southern Brazil. Pretreatment ChT activity was available for 32 patients. Allelic frequencies found for dup24, p.Gly102Ser and p.Ala442Gly were 0.14, 0.32 and 0.12, respectively. Only one patient presented reduced ChT activity (dup24 homozygous). Comparison between wild homozygous and heterozygous for dup24 showed that both differ in relation to the ChT activity before (15,230 vs 6936 nmol/h/mL, p < .001), but not after treatment (5212 vs 3045 nmol/h/mL, p = .227).

Conclusions: Pretreatment ChT activity was not correlated with clinical/biochemical features. There was a reduction of 63% in the ChT activity after 12 months on treatment (p < .001). There is no evidence that higher ChT levels are associated with a more severe symptomatology in untreated GD patients. The pretreatment ChT levels appear to be mainly dependent on the presence/absence of the dup24 allele.