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

Orphanet Journal of Rare Diseases

Neal J Weinreb³  Olaf A Bodamer²  Deborah Barbouth⁴  Marissa Orenstein¹ 

[1] Department of Medical Education, Miller School of Medicine, Miami, FL, USA;Hussman Institute of Human Genomics University of Miami, Miller School of Medicine, Miami, FL, USA;University Research Foundation for Lysosomal Storage Diseases, Inc., Northwest Oncology Hematology Associates PA, 8170 Royal Palm Boulevard, Coral Springs, FL 33065, USA;Dr John T. Macdonald Foundation Department of Human Genetics, Miller School of Medicine, Miami, FL, USA

关键词: Severity score;    Treatment outcomes;    Enzyme replacement therapy;    Natural history;    South Florida;    Genotype;    Phenotype;    Glucocerebrosidase;    Gaucher disease;   

Others  :  863220
DOI  :  10.1186/1750-1172-9-45

 received in 2014-01-23, accepted in 2014-03-13,  发布年份 2014

【 摘 要 】

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.

【 授权许可】

   
2014 Orenstein et al.; licensee BioMed Central Ltd.

【 图 表 】

【 参考文献 】

• [1]Grabowski G, Kolodny E, Weinreb N, Rosenbloom B, Prakash-Cheng A, Kaplan P, Charrow J, Pastores G, Mistry P: Gaucher Disease: Phenotypic and Genetic Variation. In The Online Metabolic and Molecular Basis of Inherited Metabolic Disease. Edited by Scriver C, Beaudet A, Valle D, Slye W. New York: McGraw-Hill Publishers; 2010. http://ommid.mhmedical.com/content.aspx?bookid=474§ionid=45374149 webcite
• [2]Sidransky E: Heterozygosity for a Mendelian disorder as a risk factor for complex disease. Clin Genet 2006, 70(4):275-282.
• [3]Lo SM, Choi M, Liu J, Jain D, Boot RG, Kallemeijn WW, Aerts JM, Pashankar F, Kupfer GM, Mane S, Lifton RP, Mistry PK: Phenotype diversity in type 1 Gaucher disease: discovering the genetic basis of Gaucher disease/hematologic malignancy phenotype by individual genome analysis. Blood 2012, 119(20):4731-4740.
• [4]Biegstraaten M, van Schaik IN, Aerts JM, Hollak CE: Non-neuronopathic. Gaucher disease reconsidered. Prevalence of neurological manifestations in a Dutch cohort of type I Gaucher disease patients and a systematic review of the literature. J Inherit Metab Dis 2008, 31:337-349.
• [5]Meikle PJ, Hopwood JJ, Clague AE, Carey WF: Prevalence of lysosomal storage disorders. JAMA 1999, 281(3):249-254.
• [6]Cox TM, Schofield JP: Gaucher’s disease: clinical features and natural history. Ballieres Clin Haematol 1997, 10:657-689.
• [7]Aharon-Peretz J, Rosenbaum H, Gershoni-Baruch R: Mutations in the glucocerebrosidase gene and Parkinson’s disease in Ashkenazi Jews. N Engl J Med 2004, 351(19):1972-1977.
• [8]Horowitz M, Pasmanik-Chor M, Borochowitz Z, Falik-Zaccai T, Heldmann K, Carmi R, Parvari R, Beit-Or H, Goldman B, Peleg L, Levy-Lahad E, Renbaum P, Legum S, Shomrat R, Yeger H, Benbenisti D, Navon R, Dror V, Shohat M, Magal N, Navot N, Eyal N: Prevalence of glucocerebrosidase mutations in the Israeli Ashkenazi Jewish population. Hum Mutat 1998, 12(4):240-244. Erratum in: Hum Mutat 1999;13(3):255
• [9]Sheskin I, Dashevsky A: Jewish population in the United States. Am Jew 2012, 6:4-46. last accessed at http://www.jewishdatabank.org/Studies/details.cfm?StudyID=611 webcite
• [10]Balwani M, Fuerstman L, Kornreich R, Edelmann L, Desnick RJ: Type 1 Gaucher disease: significant disease manifestations in “asymptomatic” homozygotes. Arch Intern Med 2010, 170(16):1463-1469. doi:10.1001/archinternmed.2010.302. Erratum in: Arch Intern Med. 2010 Nov 8;170(20):1833
• [11]Taddei TH, Kacena KA, Yang M, Yang R, Malhotra A, Boxer M, Aleck KA, Rennert G, Pastores GM, Mistry PK: The underrecognized progressive nature of N370S Gaucher disease and assessment of cancer risk in 403 patients. Am J Hematol 2009, 84(4):208-214. 10.1002/ajh.21362
• [12]Mistry PK, Sadan S, Yang R, Yee J, Yang M: Consequences of diagnostic delays in type 1 Gaucher disease: the need for greater awareness among hematologists-oncologists and an opportunity for early diagnosis and intervention. Am J Hematol 2007, 82:697-701.
• [13]Giraldo P, Alfonso P, Irún P, Gort L, Chabás A, Vilageliu L, Grinberg D, Sá Miranda CM, Pocovi M: Mapping the genetic and clinical characteristics of Gaucher disease in the Iberian Peninsula. Orphanet J Rare Dis 2012, 7:17. 10.1186/1750-1172-7-17 BioMed Central Full Text
• [14]Stirnemann J, Vigan M, Hamroun D, Heraoui D, Rossi-Semerano L, Berger MG, Rose C, Camou F, de Roux-Serratrice C, Grosbois B, Kaminsky P, Robert A, Caillaud C, Froissart R, Levade T, Masseau A, Mignot C, Sedel F, Dobbelaere D, Vanier MT, Valayanopoulos V, Fain O, Fantin B, de Villemeur TB, Mentré F, Belmatoug N: The French Gaucher’s disease registry: clinical characteristics, complications and treatment of 562 patients. Orphanet J Rare Dis 2012, 7:77. 10.1186/1750-1172-7-77 BioMed Central Full Text
• [15]Drelichman G, Linares A, Villalobos J, Cabello JF, Kerstenetzky M, Kohan RM, Martins AM: Gaucher disease in Latin America. A report from the Gaucher Disease International Registry and the Latin American Group for Gaucher Disease. Medicina (B Aires) 2012, 72(4):273-282.
• [16]Charrow J, Andersson HC, Kaplan P, Kolodny EH, Mistry P, Pastores G, Rosenbloom BE, Scott CR, Wappner RS, Weinreb NJ, Zimran A: The Gaucher registry: demographics and disease characteristics of 1698 patients with Gaucher disease. Arch Intern Med 2000, 160(18):2835-2843.
• [17]Weinreb NJ, Cappellini MD, Cox TM, Giannini EH, Grabowski GA, Hwu WL, Mankin H, Martins AM, Sawyer C, Vom Dahl S, Yeh MS, Zimran A: A validated disease severity scoring system for Gaucher disease type 1. Genet Med 2009, 12:1-8.
• [18]Weinreb NJ, Taylor J, Cox T, Yee J, Vom DS: A benchmark analysis of the achievement of therapeutic goals for type 1 Gaucher disease patients treated with imiglucerase. Am J Hematol 2008, 83:890-895.
• [19]Ogburn RF: Demographic and Economic Characteristics of Southeast Florida. South Florida Regional Planning Council; 2012. http://www.sfrpc.com/Dick%27s%20Demographics/SEFloridaMay12_Full.pdf webcite; last accessed September 16, 2013
• [20]Rosenbloom BE, Weinreb NJ, Zimran A, Kacena KA, Charrow J, Ward E: Gaucher disease and cancer incidence: a study from the Gaucher Registry. Blood 2005, 105(12):4569-4572.
• [21]de Fost M, Vom Dahl S, Weverling GJ, Brill N, Brett S, Häussinger D, Hollak CE: Increased incidence of cancer in adult Gaucher disease in Western Europe. Blood Cells Mol Dis 2006, 36(1):53-58.
• [22]Costello R, O’Callaghan T, Sébahoun G: Gaucher disease and multiple myeloma. Leuk Lymphoma 2006, 47(7):1365-1368.
• [23]Ayto R, Hughes DA: Gaucher disease and myeloma. Crit Rev Oncog 2013, 18(3):247-268.
• [24]Elstein D, Scott CR, Zeigler M, Abrahamov A, Zimran A: Phenotypic heterogeneity in patients with Gaucher disease and the N370S/V394L genotype. Genet Test 2005, 9(1):26-29.
• [25]Gan-Or Z, Giladi N, Rozovski U, Shifrin C, Rosner S, Gurevich T, Bar-Shira A, Orr-Urtreger A: Genotype-phenotype correlations between GBA mutations and Parkinson disease risk and onset. Neurology 2008, 70(24):2277-2283.
• [26]Fairley C, Zimran A, Phillips M, Cizmarik M, Yee J, Weinreb N, Packman S: Phenotypic heterogeneity of N370S homozygotes with type I Gaucher disease: an analysis of 798 patients from the ICGG Gaucher registry. J Inherit Metab Dis 2008, 31:738-744.
• [27]Weinreb NJ, Goldblatt J, Villalobos J, Charrow J, Cole JA, Kerstenetzky M, Vom Dahl S, Hollak C: Long-term clinical outcomes in type 1 Gaucher disease following 10 years of imiglucerase treatment. J Inherit Metab Dis 2013, 36(3):543-553.
• [28]Hughes DA, Al-Sayed M, Belmatoug N, Bodamer O, Böttcher T, Cappellini M, Cohen IJ, Eagleton T, Elstein D, Giraldo P, Jones S, Kaplinsky C, Lund A, Machaczka M, Mengel E, Pastores GM, Rosenbaum H, Sjo M, Tiling N, Tsaftaridis P, Zimran A, Weinreb N: Early access experience with VPRIV(®): recommendations for ‘core data’ collection. Blood Cells Mol Dis 2011, 47(2):140-142. 10.1016/j.bcmd.2010.10.015
• [29]Black N: Why we need observational studies to evaluate the effectiveness of health care. BMJ 1996, 312(7040):1215-1218.
• [30]Resnick D, Bozic KJ: Meta-analysis of trials of recombinant human bone morphogenetic protein-2: what should spine surgeons and their patients do with this information? Ann Intern Med 2013, 158:912-913. 10.7326/0003-4819-158-12-201306180-00010
• [31]Sidransky E: Gaucher disease: complexity in a “simple” disorder. Mol Genet Metab 2004, 83:6-15.
• [32]Snyder CF, Aaronson NK, Choucair AK, Elliott TE, Greenhalgh J, Halyard MY, Hess R, Miller DM, Reeve BB, Santana M: Implementing patient-reported outcomes assessment in clinical practice: a review of the options and considerations. Qual Life Res 2012, 21:1305-1314. doi:10.1007/s11136-011-0054-x