Gaucher disease in Romanian patients: incidence of the most common mutations and phenotypic manifestations

Abstract

Gaucher disease (GD) is an inherited glycolipid storage disorder resulting from the deficiency of glucocerebrosidase. It is the most frequent lysosomal storage disease in Romania, accounting for 70% of all lysosomal disorders diagnosed since 1997 in this country. The prevalence of six common mutations (N370S, L444P, R463C, 84GG, recNciI and recTL) and their phenotypic impact were studied in 20 type 1 GD patients of non-Jewish origin. Mutation analysis identified 77.8% of the GD alleles. The N370S mutation had the highest prevalence (50%), followed by the L444P (22.2%) and the recNciI (5.6%) alleles. Mutations R463C, 84GG and recTL have not been found in our patients. Rare or novel mutations likely accounted for 22.2% of the disease-producing uncharacterised alleles. Our study indicates a high prevalence of type 1 among Romanian GD patients. Clinical phenotype and disease severity were evaluated according to the standardised severity score index. Genotype -phenotype correlations were similar to those reported for other Caucasian non-Jewish populations. The absence of neuronopathic disease in patients presenting at least one copy of the N370S allele was confirmed, but the relative mildness of N370S homozygotes was not a constant feature among our patients. The presence of the L444P or of uncharacterised sporadic mutations was always associated with severe clinical manifestations, even in compound heterozygotes with the N370S allele. A large degree of phenotypic variability was observed in patients displaying the same genotype. The particularities of genotype -phenotype correlations may suggest the impact of other genetic or non-genetic factors on the clinical picture.

The clinical effectiveness and cost-effectiveness of enzyme replacement therapy for Gaucher's disease: a systematic review

“…124 The patients were drawn from all over Romania; however, no information is given to indicate how representative the sample is of the Romanian population. The mean age at diagnosis was not reported; the mean age at evaluation was 24.2 years (SE 3.18).…”

The clinical effectiveness and cost-effectiveness of enzyme replacement therapy for Gaucher’s disease: a systematic review

“…71,[124][125][126] Further follow-up data on 23 of these patients were reported by Beutler and colleagues. 71 With an average of 3 years' further follow-up, 16 patients had not progressed further, four patients had increased their SSI by 1 point and three patients had progressed by more than 1 point.…”

“…Drugan and colleagues report the clinical characteristics of 20 type I Gaucher's disease patients. 124 The patients were drawn from all over Romania; however, no information is given to indicate how representative the sample is of the Romanian population. The mean age at diagnosis was not reported; the mean age at evaluation was 24.2 years (SE 3.18).…”

“…17,71,[124][125][126] This information can be used to construct a natural history data set. Those studies that reported the SSI and age at two time-points provided two observations for the natural history data set.…”

“…17,54,71,89,[124][125][126][127][128][129][130][131][132][133][134][135] In addition, 15 papers that focused on one clinical domain or the relationship between two clinical domains were identified. Five of these concerned skeletal complications, four considered the relationship between skeletal and visceral symptoms, including the impact of splenectomy, and the remainder considered skeletal symptoms in isolation, pulmonary symptoms, growth retardation or pregnancy in Gaucher's disease.…”