Patients with type 1 Gaucher disease in South Florida, USA: demographics, genotypes, disease severity and treatment outcomes

Abstract

BackgroundGaucher 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.MethodsNinety-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.ResultsThe 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%).ConclusionsDemographic 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.

Gaucher Disease in Ontario, Canada: Clinical Manifestations, Natural Progression, and Treatment Response

“…The most common ethnic origins in Ontario are Canadians, followed by English, Scottish, and Irish 40 . Accordingly, this patient cohort has similar genotype composition when compared to the United Kingdom/ Ireland population: N370S/N370S (29.4% vs. 30.3%) and N370S/other 36.5% vs. 40.0%), except for N370S/L444P (21.2% vs. 3.3%) 30 . Similarities were also observed when compared to the World ICGG Registry, in N370S/N370S (29.4% vs. 24.0%) and N370S/L444P (21.2% vs. 18.1%), except for N370S/other ( 36.5% vs. 46.7%) 30 .…”

“…There have been several studies examining the epidemiological profiles of GD in specific regions such as France 21 , Brazil 29 , Iberia 9 , and South Florida 30 , but none in Canada. Ontario is the highest populated province in Canada, consisting of 38.5% of the population 31 , the largest share (53.3%) of immigrants 32 , and more than half (57.9%) of Ashkenazi Jews 33 .…”

Non-immune Hemolysis in Gaucher Disease and Review of the Literature

“…Additionally, the diagnosis of GD in many of these cases was based solely on the visualization of Gaucher cells, which can be difficult to distinguish from pseudo-Gaucher cells present in other diseases. 3 Wasserman et al (writing in 1955) were the first to report of Coombs-positive hemolytic anemia in GD, 22 which was followed by several case series consistent with a 0.55%-2.7% rate of AIHA in GD patients 10,27,[29][30][31] and several additional cases (Table 1). 4,32 Autoimmune hemolytic anemia (AIHA) is reported to be more common in GD patients than in the general population, which has an annual incidence of 1 in 100,000 (0.001%).…”

Gaucher disease epidemiology and natural history: a comprehensive review of the literature

“…In the largest (n = 8069), 0.11% of the population were homozygous for any mutation, the majority of which were N370S/N370S genotypes (0.10%); 6.5% were identified as a carrier of a GD genotype, most of which had an N370S mutation (6%) [41]. In a fifth study that retrieved the records of 93 South Florida patients with GD1 from the International Collaborative Gaucher Group (ICGG) Gaucher Registry, 61.9% were shown to be homozygous for the N370S mutation [43]. These findings are most likely a consequence of the large AJ population of South Florida.…”

“…In one study, age at GD1 diagnosis was reported by genotype: mean age at diagnosis was older than 10 years for patients with genotypes N370S/?, N370S/N370S, N370S/L444P, and N370S/rare allele; age at diagnosis of younger than 10 years was reported in patients with N370S/ 84GG, L444P/L444P, L444P/?, and N370S/IVS2+1 genotypes all of which are often associated with severe GD symptomatology [3]. Three additional studies reported a mean age at diagnosis ranging from 6 years in the Moroccan study of 11 patients to 50 years in 93 patients from South Florida included in the ICGG Gaucher Registry [43,44]; the Moroccan study also identified two cases of GD2 diagnosed at 3 months and 18 months, respectively; age at diagnosis of seven GD3 cases ranged from 10 months to 2 years and 7 months in a study of Taiwanese patients [58]. In a multinational observational study (24-month study duration) enrolling all non-Ashkenazi patients (who had been seen for a hematological evaluation), the mean age at diagnosis was 32.6 years [60].…”