<abstract xmlns="http://www.w3.org/1999/xhtml"><p> Background: Gaucher disease (GD) is caused by a recessively inherited deficiency of glucocerebrosidase which is encoded by the GBA gene in which nearly 450 mutations have been described. However, only a few genotype- phenotype correlations have been clearly established. The aim of this study was to investigate molecular features of GD in Romanian patients and to evaluate their impact on treatment response. Material and methods: 69 patients, diagnosed between 1997 and 2014 at our national referral laboratory, were included in this study. Frequent point mutations (N370S, L444P, 84GG, R463C) were detected by amplification and restriction enzyme digestion. Recombinant alleles (recTL, recNciI, recA456P) were screened by DNA sequencing. Plasma chitotriosidase served as a biomarker of disease severity throughout the follow-up period. Results: 66 patients had the non-neuronopathic (type 1) form of GD and 3 had the chronic neuronopathic (type 3) phenotype. We identified 79% of the mutant alleles, among which the most frequent mutations were N370S (54%) and L444P (18%). We found a statistically significant (p&lt;0.001) and moderate to good correlation between the total therapeutic dose and the residual chitotriosidase activity (R = 0.621). After two years of treatment, we noticed statistically significant variations in chitotriosidase activity corresponding to the most frequent genotypes (N370S/ unknown allele, N370S/L444P, N370S/N370S and N370S/R463Q). Conclusions: Allele distribution displayed specific features in Romanian GD patients, such as the high prevalence of the N370S allele. Chitotriosidase activity measurement allowed the investigation of genotype influence on treatment outcome.</p></abstract>

Background: Gaucher disease (GD) is caused by a recessively inherited deficiency of glucocerebrosidase which is encoded by the GBA gene in which nearly 450 mutations have been described. However, only a few genotype- phenotype correlations have been clearly established. The aim of this study was to investigate molecular features of GD in Romanian patients and to evaluate their impact on treatment response. Material and methods: 69 patients, diagnosed between 1997 and 2014 at our national referral laboratory, were included in this study. Frequent point mutations (N370S, L444P, 84GG, R463C) were detected by amplification and restriction enzyme digestion. Recombinant alleles (recTL, recNciI, recA456P) were screened by DNA sequencing. Plasma chitotriosidase served as a biomarker of disease severity throughout the follow-up period. Results: 66 patients had the non-neuronopathic (type 1) form of GD and 3 had the chronic neuronopathic (type 3) phenotype. We identified 79% of the mutant alleles, among which the most frequent mutations were N370S (54%) and L444P (18%). We found a statistically significant (p<0.001) and moderate to good correlation between the total therapeutic dose and the residual chitotriosidase activity (R = 0.621). After two years of treatment, we noticed statistically significant variations in chitotriosidase activity corresponding to the most frequent genotypes (N370S/ unknown allele, N370S/L444P, N370S/N370S and N370S/R463Q). Conclusions: Allele distribution displayed specific features in Romanian GD patients, such as the high prevalence of the N370S allele. Chitotriosidase activity measurement allowed the investigation of genotype influence on treatment outcome.

Laboratory diagnosis and follow-up of Romanian Gaucher disease patients

Revista Romana de Medicina de Laborator

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 License.

{"article-title":"Laboratory diagnosis and follow-up of Romanian Gaucher disease patients"}

Background: Gaucher disease (GD) is caused by a recessively inherited deficiency of glucocerebrosidase which is encoded by the GBA gene in which nearly 450...

Laboratory diagnosis and follow-up of Romanian Gaucher disease patients

Article Category: Original Research

Publicado en línea: 01 ago 2017

Páginas: 275 - 285

Recibido: 26 feb 2017

Aceptado: 03 may 2017

DOI: https://doi.org/10.1515/rrlm-2017-0018

Palabras clave
Gaucher disease, genotype-phenotype correlations, chitotriosidase, enzyme replacement therapy, Romanian population

© by Tudor Drugan

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 License.

Laboratory diagnosis and follow-up of Romanian Gaucher disease patients

Article Category: Original Research

Publicado en línea: 01 ago 2017

Páginas: 275 - 285

Recibido: 26 feb 2017

Aceptado: 03 may 2017

DOI: https://doi.org/10.1515/rrlm-2017-0018

Palabras claveGaucher disease, genotype-phenotype correlations, chitotriosidase, enzyme replacement therapy, Romanian population

© by Tudor Drugan

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 License.

Palabras clave
Gaucher disease, genotype-phenotype correlations, chitotriosidase, enzyme replacement therapy, Romanian population