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

Orenstein M, Barbouth D, Bodamer OA, Weinreb NJ - Orphanet J Rare Dis (2014)

Bottom Line: 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.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).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%).

View Article: PubMed Central - HTML - PubMed

Affiliation: Dr John T, Macdonald Foundation Department of Human Genetics, Miller School of Medicine, Miami, FL, USA. boneal@winning.com.

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.

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DS3 scores (Y axis) per GBA genotypes in 89 South Florida patients with GD1.
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Figure 2: DS3 scores (Y axis) per GBA genotypes in 89 South Florida patients with GD1.

Mentions: For the 88 patients with known genotypes, sufficient information to calculate baseline DS3 scores was available for 81 patients. DS3 scores in N370S homozygous patients (N = 48) were highly variable but generally in the mild to moderate range (Table 3). Because of small numbers of patients in each sub-group, the only genotype with a statistically significant difference in DS3 score from N370S/N370S was N370S/L444P (N = 10) in which severity was generally severe. Severity was also significantly higher when N370S/84GG patients (N = 4) are grouped with the N370S/L444P patients. The broad range of genotypes and disease severity in South Florida patients is shown is shown in Figure 2 which emphasizes the highly variable severity scores in N370S homozygous patients with approximately half the patients falling within the moderate to marked severity range.


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

Orenstein M, Barbouth D, Bodamer OA, Weinreb NJ - Orphanet J Rare Dis (2014)

DS3 scores (Y axis) per GBA genotypes in 89 South Florida patients with GD1.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4230272&req=5

Figure 2: DS3 scores (Y axis) per GBA genotypes in 89 South Florida patients with GD1.
Mentions: For the 88 patients with known genotypes, sufficient information to calculate baseline DS3 scores was available for 81 patients. DS3 scores in N370S homozygous patients (N = 48) were highly variable but generally in the mild to moderate range (Table 3). Because of small numbers of patients in each sub-group, the only genotype with a statistically significant difference in DS3 score from N370S/N370S was N370S/L444P (N = 10) in which severity was generally severe. Severity was also significantly higher when N370S/84GG patients (N = 4) are grouped with the N370S/L444P patients. The broad range of genotypes and disease severity in South Florida patients is shown is shown in Figure 2 which emphasizes the highly variable severity scores in N370S homozygous patients with approximately half the patients falling within the moderate to marked severity range.

Bottom Line: 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.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).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%).

View Article: PubMed Central - HTML - PubMed

Affiliation: Dr John T, Macdonald Foundation Department of Human Genetics, Miller School of Medicine, Miami, FL, USA. boneal@winning.com.

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.

Show MeSH
Related in: MedlinePlus