title: Phenotypic and genotypic heterogeneity in Gaucher disease type 1: a comparison between Brazil and the rest of the world.
abstract: Type 1 Gaucher disease, the most common lysosomal storage disorder, results from deficiency of glucocerebrosidase causing pathologic accumulation of glucocerebroside. The disease is characterized by marked variation in age of onset and degree of anemia, thrombocytopenia, hepatosplenomegaly, and skeletal disease. Most published data on Gaucher disease come from populations with large proportions of Ashkenazi-Jewish patients, who tend to have less severe disease. We compared selected demographic, clinical, and genetic parameters for Brazilian (N = 221) and rest-of-world (N = 1477) type 1 Gaucher disease patients entered into the ICGG Gaucher Registry since 1991. We also compared Brazilian patients to non-Ashkenazi rest-of-world patients (N = 692) to determine if differences were the result of fewer Brazilian Ashkenazi-Jewish patients (0.5% vs 45.0%). The Brazilian cohort differed significantly (p < 0.05) from the rest-of-world and rest-of-world non-Ashkenazi cohort, respectively, in the following measures: higher proportion of females (59.7% vs 50.4% and 49.7%), lower mean age at diagnosis (17.1 vs 24.1 and 18.8), and higher proportions of patients with anemia (55.5% vs 29.9% and 35.7%), bone pain (57.7% vs 33.7% and 35%), bone crises (16.1% vs 6.5% and 7.4%), and lytic lesions (17.0% vs 7.6% and 7.4%). The most common genotype in Brazil was N370S/L444P (c1448T-->C/c1226A-->C) (46.8% versus 16.3% and 25.7%). These data highlight the genetic and phenotypic heterogeneity among geographic populations of type 1 Gaucher patients and suggest that as a group, Brazilian patients may have a more aggressive form of the disease than rest-of-world patients. The findings also emphasize the need for caution in making generalizations about Gaucher disease across demographic groups.
authors.affiliation: FCM Santa Casa de São Paulo, São Paulo, SP, Brazil.
authors.forename: Elisa
authors.initials: E
authors.lastname: Sobreira
authors.forename: Ricardo F
authors.initials: RF
authors.lastname: Pires
authors.forename: Marta
authors.initials: M
authors.lastname: Cizmarik
authors.forename: Gregory A
authors.initials: GA
authors.lastname: Grabowski
mesh_terms: D000293:Adolescent; D000328:Adult; D001938:Brazil / Q000208:ethnology; D002648:Child; D015331:Cohort Studies; D005260:Female; D005776:Gaucher Disease / Q000145:classification* / Q000175:diagnosis / Q000235:genetics*; D018740:Genetic Heterogeneity; D005838:Genotype; D005962:Glucosylceramidase / Q000235:genetics*; D006801:Humans; D007585:Jews / Q000235:genetics; D008297:Male; D010641:Phenotype
chemical_list: D005962:Glucosylceramidase