title: Patients with type 1 Gaucher disease in South Florida, USA: demographics, genotypes, disease severity and treatment outcomes.
abstract: BACKGROUND
  Gaucher disease, an autosomal recessive condition due to deficiency of lysosomal glucocerebrosidase, is a multisystemic disease, with variable age of onset, severity and progression. It is classified into subtypes delineated by the absence (type 1) or presence (type 2 and 3) of primary nervous system involvement. The ethnically diverse, largely immigrant population in South Florida has a spectrum of Gaucher disease phenotypes, creating a challenge for optimization of disease management and an opportunity to explore treatment patterns.
  
  
  METHODS
  Ninety-three records from patients with Gaucher type I in South Florida were retrieved from the International Collaborative Gaucher Group (ICGG) Registry. Individual genotypes were correlated with severity scores and success at achieving published therapeutic goals for haemoglobin concentration, platelet count, spleen volume, liver volume and amelioration of bone pain and bone crises.
  
  
  RESULTS
  The majority of patients were diagnosed during the fifth decade of life. Almost two-thirds were homozygous for the N370S mutation, reflecting the large Ashkenazi Jewish population in South Florida. The majority received imiglucerase (62.8%) at various intervals. 24.5% of patients underwent splenectomy before starting enzyme replacement therapy. After a median 12 treatment years, South Florida patients matched or exceeded the ICCG 4 year therapeutic goal achievement for platelet count (85.4% vs. 79.6% success), spleen volume (93.3% vs. 78.0% success), liver volume (93.4% vs. 90.6% success), and bone crises (100% vs. 99% success). Nevertheless, fewer patients with intact spleens had sustained achievement of all 6 therapeutic goals (30.4% versus 41.4%) and only 40% of the splenectomy patients sustained achievement of 5/5 possible goals. 54.7% of the intact spleen patients continued to have bone pain vs. 29.8% in ICCG. Significantly, only 37% of the ICGG patient cohort had bone pain prior to initiation of treatment compared to 73.4% of the South Florida patients (moderate or severe pain in 59.6%).
  
  
  CONCLUSIONS
  Demographic characteristics are a significant determinant of the differences in response to treatment observed in South Florida Gaucher patients compared to those described in the international population enrolled in the ICGG Gaucher Registry. Individual genotypes and ethnic background are important considerations for optimizing patient care for Gaucher disease.
authors.forename: Marissa
authors.initials: M
authors.lastname: Orenstein
authors.forename: Deborah
authors.initials: D
authors.lastname: Barbouth
authors.forename: Olaf A
authors.initials: OA
authors.lastname: Bodamer
authors.affiliation: Dr John T, Macdonald Foundation Department of Human Genetics, Miller School of Medicine, Miami, FL, USA. boneal@winning.com.
authors.forename: Neal J
authors.initials: NJ
authors.lastname: Weinreb
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D056947:Enzyme Replacement Therapy; D005260:Female; D005431:Florida; D005776:Gaucher Disease / Q000188:drug therapy / Q000453:epidemiology* / Q000235:genetics*; D005838:Genotype; D005962:Glucosylceramidase / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged
chemical_list: D005962:Glucosylceramidase