The Journal of Pediatrics
Volume 155, Issue 4, Supplement , Pages S10-S18 , October 2009

Recommendations on Diagnosis, Treatment, and Monitoring for Gaucher Disease

  • Ana Maria Martins, MD, PhD

      Affiliations

    • Centro de Referência em Erros Inatos, Universidade Federal de São Paulo, São Paulo, Brazil
    • Corresponding Author InformationReprint requests: Ana Maria Martins, Rua Joaquim Antunes, 620/72, CEP 05415-010–São Paulo, SP.
  • ,
  • Eugenia Ribeiro Valadares, MD, PhD

      Affiliations

    • Departamento de Propedêutica Complementar da Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil
  • ,
  • Gilda Porta, MD, PhD

      Affiliations

    • Unidade Hepatologia Pediátrica, Hospital de Clinicas Instituto da Criança, Faculdade de Medicina da Universidade Federal de São Paul, São Paulo, Brazil
  • ,
  • Janice Coelho, PhD

      Affiliations

    • Departamento de Bioquímica – ICBS, Universidade Federal do Rio Grande do Sul e Serviço de Genética do Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil
  • ,
  • José Semionato Filho, MD

      Affiliations

    • Centro Geral Pediátrica, Hospital da Fundação do Estado de Minas Gerais (FHEMIG), Minas Gerais, Brazil
  • ,
  • Mara Albonei Dudeque Pianovski, PhD

      Affiliations

    • Disciplina de Hematologia e Oncologia do Departamento Pediátrica, Universidade Federal do Paraná, Paraná, Brazil
  • ,
  • Marcelo Soares Kerstenetzky, MD

      Affiliations

    • Serviço de Hepatologia Infantil do Hospital da Restauração, Pernambuco, Brazil
  • ,
  • Maria de Fátima Pombo Montoril, MD

      Affiliations

    • Fundação de Hemoterapia e Hamatologia Central do Pará, Pará, Brazil
  • ,
  • Paulo Cesar Aranda, MD

      Affiliations

    • Serviço de Hematologia do Hospital Evangélico de Londrina, Paraná, Brazil
  • ,
  • Ricardo Flores Pires, MD

      Affiliations

    • Clínica Dr. Ricardo Pires para Doenças Metabólicas, Porto Alegre, Brazil
  • ,
  • Ronald Moura Vale Mota, MD

      Affiliations

    • Serviço de Ortopedia Pediátrica, Hospital Socor Geral, Minas Gerais, Brazil
  • ,
  • Teresa Cristina Bortolheiro, MD

      Affiliations

    • Disciplina de Hematologia e Oncologia da Faculdade de Serviços Médicos da Santa Casa de São Paulo, São Paulo, Brazil
  • ,
  • Brazilian Study Group on Gaucher Disease and other Lysosomal Storage Diseases

      Affiliations

    • The Brazilian Study Group on Gaucher Disease and other Lysosomal Storage Diseases is independent, and received financial support from Genzyme do Brasil for the holding of meetings by the group. The opinions or views expressed in this article are those of the authors and do not necessarily reflect the opinions or recommendations of Genzyme Brasil.

References 

  1. Meikle PJ, Hopwood JJ. Lysosomal storage disorders: emerging therapeutic options require early diagnosis. Eur J Pediatr. 2003;162(Suppl 1):S34–S37
  2. Grabowski GA. Gaucher disease: lessons from a decade of therapy. J Pediatr. 2004;144:S15–S19
  3. Beutler E, Grabowski G. Gaucher Disease. In:  Scriver C,  Sly W,  Childs B, et al. editor. The metabolic and molecular bases of inherited disease. New York: McGraw-Hill; 2000;p. 3663–3668
  4. Nilsson O, Svennerholm L. Accumulation of glucosylceramide and glucosylsphingosine (psychosine) in cerebrum and cerebellum in infantile and juvenile Gaucher disease. J Neurochem. 1982;39:709–718
  5. Schiffmann R, Heyes MP, Aerts JM, Dambrosia JM, Patterson MC, DeGraba T, et al. Prospective study of neurological responses to treatment with macrophage-targeted glucocerebrosidase in patients with type 3 Gaucher's disease. Ann Neurol. 1997;42:613–621
  6. Wong K, Sidransky E, Verma A, Mixon T, Sandberg GD, Wakefield LK, et al. Neuropathology provides clues to the pathophysiology of Gaucher disease. Mol Genet Metab. 2004;82:192–207
  7. Barranger J, Rice O. Gaucher disease: diagnosis, monitoring, and management. Gaucher Clin Perspect. 1997;5:1–6
  8. Grabowski GA, Leslie N, Wenstrup R. Enzyme therapy for Gaucher disease: the first 5 years. Blood Rev. 1998;12:115–133
  9. Incerti C. Gaucher disease: an overview. Semin Hematol. 1995;32:3
  10. Charrow J, Esplin JA, Gribble TJ, Kaplan P, Kolodny EH, Pastores GM, et al. Gaucher disease: recommendations on diagnosis, evaluation, and monitoring. Arch Intern Med. 1998;158:1754–1760
  11. Weinreb NJ, Aggio MC, Andersson HC, Andria G, Charrow J, Clarke JT, et al. Gaucher disease type 1: revised recommendations on evaluations and monitoring for adult patients. Semin Hematol. 2004;41:15–22
  12. Charrow J, Andersson HC, Kaplan P, Kolodny EH, Mistry P, Pastores G, et al. Enzyme replacement therapy and monitoring for children with type 1 Gaucher disease: consensus recommendations. J Pediatr. 2004;144:112–120
  13. Andersson HC, Charrow J, Kaplan P, Mistry P, Pastores GM, Prakash-Cheng A, et al. Individualization of long-term enzyme replacement therapy for Gaucher disease. Genet Med. 2005;7:105–110
  14. vom Dahl S, Poll L, Di Rocco M, Ciana G, Denes C, Mariani G, et al. Evidence-based recommendations for monitoring bone disease and the response to enzyme replacement therapy in Gaucher patients. Curr Med Res Opin. 2006;22:1045–1064
  15. Martins AM, Lobo CL, Sobreira EAP, et al. Tratamento da doença de Gaucher: um consenso brasileiro. Rev Bras Hematol Hemoter. 2003;25:89–95
  16. Sidransky E. Gaucher disease: complexity in a “simple” disorder. Mol Genet Metab. 2004;83:6–15
  17. Altarescu G, Schiffmann R, Parker CC, Moore DF, Kreps C, Brady RO, et al. Comparative efficacy of dose regimens in enzyme replacement therapy of type I Gaucher disease. Blood Cells Mol Dis. 2000;26:285–290
  18. Gaucher disease . Current issues in diagnosis and treatment. NIH Technology Assessment Panel on Gaucher Disease. JAMA. 1996;275:548–553
  19. Zimran A, Gelbart T, Westwood B, Grabowski GA, Beutler E. High frequency of the Gaucher disease mutation at nucleotide 1226 among Ashkenazi Jews. Am J Hum Genet. 1991;49:855–859
  20. Hollak CE, Levi M, Berends F, Aerts JM, van Oers MH. Coagulation abnormalities in type 1 Gaucher disease are due to low-grade activation and can be partly restored by enzyme supplementation therapy. Br J Haematol. 1997;96:470–476
  21. Charrow J, Andersson HC, Kaplan P, Kolodny EH, Mistry P, Pastores G, et al. The Gaucher registry: demographics and disease characteristics of 1698 patients with Gaucher disease. Arch Intern Med. 2000;160:2835–2843
  22. Weinreb NJ, Charrow J, Andersson HC, Kaplan P, Kolodny EH, Mistry P, et al. Effectiveness of enzyme replacement therapy in 1028 patients with type 1 Gaucher disease after 2 to 5 years of treatment: a report from the Gaucher Registry. Am J Med. 2002;113:112–119
  23. McHugh K, Olsen ØE Vellodi A. Gaucher disease in children: radiology of non-central nervous system manifestations. Clin Radiol. 2004;59:117–123
  24. Barranger JA, O'Rourke E. Lessons learned from the development of enzyme therapy for Gaucher disease. J Inherit Metab Dis. 2001;24(Suppl 2):89–96discussion 87-8
  25. Weinreb N, Lee R. Changing patterns of mortality in Gaucher disease prior to and following the advent of enzyme replacement therapy. Blood. 2004;11:Abstract 3799
  26. Mignot C, Doummar D, Maire I, De Villemeur TB. Type 2 Gaucher disease: 15 new cases and review of the literature. Brain Dev. 2006;28:39–48
  27. Sidransky E, Fartasch M, Lee RE, Metlay LA, Abella S, Zimran A, et al. Epidermal abnormalities may distinguish type 2 from type 1 and type 3 of Gaucher disease. Pediatr Res. 1996;39:134–141
  28. Stone DL, van Diggelen OP, de Klerk JB, Gaillard JL, Niermeijer MF, Willemsen R, et al. Is the perinatal lethal form of Gaucher disease more common than classic type 2 Gaucher disease?. Eur J Hum Genet. 1999;7:505–509
  29. Vellodi A, Bembi B, de Villemeur TB, Collin-Histed T, Erikson A, Mengel E, et al. Management of neuronopathic Gaucher disease: a European consensus. J Inherit Metab Dis. 2001;24:319–327
  30. Altarescu G, Hill S, Wiggs E, Jeffries N, Kreps C, Parker CC, et al. The efficacy of enzyme replacement therapy in patients with chronic neuronopathic Gaucher's disease. J Pediatr. 2001;138:539–547
  31. Sirrs S, Irving J, McCauley G, Gin K, Munt B, Pastores G, et al. Failure of resting echocardiography and cardiac catheterization to identify pulmonary hypertension in two patients with type I Gaucher disease. J Inherit Metab Dis. 2002;25:131–132
  32. Esplin J. Overview: Gaucher disease. Gaucher Clin Perspect. 1994;2:1–5
  33. Barranger J, Rice E. An overview of Gaucher disease. Gaucher Clin Perspect. 1993;1:1–5
  34. James SP, Stromeyer FW, Chang C, Barranger JA. Liver abnormalities in patients with Gaucher's disease. Gastroenterology. 1981;80:126–133
  35. Lee R. The pathology of Gaucher disease. In:  Desnick R editors. Gaucher disease a century of delineation and research. Baltimore: John Wiley & Sons; 1982;p. 177–217
  36. Platzker Y, Fisman EZ, Pines A, Kellermann JJ. Unusual echocardiographic pattern in Gaucher's disease. Cardiology. 1985;72:144–146
  37. Torloni MR, Franco K, Sass N. Gaucher's disease with myocardial involvement in pregnancy. Sao Paulo Med J. 2002;120:90–92
  38. Hollak C. Renal involvement in type 1 Gaucher disease. Gaucher Clin Perspect. 1998;6:14–15
  39. Santoro D, Rosenbloom BE, Cohen AH. Gaucher disease with nephrotic syndrome: response to enzyme replacement therapy. Am J Kidney Dis. 2002;40:E4
  40. Clarke J. Gaucher disease: differential diagnosis. Gaucher Clin Perspect. 1997;5:6–12
  41. Lewin A, Orvisky E, Goker-Alpan O, LaMarca ME, Sidransky E. Glucocerebrosidase mutations in subjects with parkinsonism. Mol Genet Metab. 2004;81:70–73
  42. Tayebi N, Callahan M, Madike V, Stubblefield BK, Orvisky E, Krasnewich D, et al. Gaucher disease and parkinsonism: a phenotypic and genotypic characterization. Mol Genet Metab. 2001;73:313–321
  43. 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;105:4569–4572
  44. Costello R, O'Callaghan T, Sébahoun G. Gaucher disease and multiple myeloma. Leuk Lymphoma. 2006;47:1365–1368
  45. Landgren O, Turesson I, Gridley G, Caporaso NE. Risk of malignant disease among 1525 adult male US Veterans with Gaucher disease. Arch Intern Med. 2007;167:1189–1194
  46. Cheung WY, Greenberg CR, Bernstein K, Schacter B, Fourie T, Seftel MD. Type I Gaucher disease following chemotherapy for light chain multiple myeloma. Intern Med. 2007;46:1255–1258
  47. Hughes D, Cappellini MD, Berger M, Droogenbroeck JV, De Fost M, Janic D, et al. Recommendations for the management of the haematological and onco-haematological aspects of Gaucher disease. Br J Haematol. 2007;138:676–686
  48. Michelin K, Wajner A, Goulart Lda S, Fachel AA, Pereira ML, de Mello AS, et al. Biochemical study on beta-glucosidase in individuals with Gaucher's disease and normal subjects. Clin Chim Acta. 2004;343:145–153
  49. Hollak CE, van Weely S, van Oers MH, Aerts JM. Marked elevation of plasma chitotriosidase activity. A novel hallmark of Gaucher disease. J Clin Invest. 1994;93:1288–1292
  50. Cabrera-Salazar MA, O'Rourke E, Henderson N, Wessel H, Barranger JA. Correlation of surrogate markers of Gaucher disease. Implications for long-term follow up of enzyme replacement therapy. Clin Chim Acta. 2004;344:101–107
  51. Sobreira E, Pires RF, Cizmarik M, Grabowski GA. Phenotypic and genotypic heterogeneity in Gaucher disease type 1: A comparison between Brazil and the rest-of-the-world. Mol Genet Metab. 2007;90:81–86
  52. Kolodny E, Tenembaum L. Storage diseases of the reticuloendothelial system. In:  Nathan D,  Oski F editor. Hematology of infancy and childhood. Philadelphia: WB Saunders; 1992;p. 1452–1491
  53. Pentchev P, Vanier M, Suzuki K, Patterson M. Niemann-Pick disease type C: a cellular cholesterol lipidosis. In:  Scriver C,  Beaudet A,  Sly W,  Valle D editor. The metabolic and molecular basis of inherited disease. New York: McGraw-Hill; 1995;p. 2625–2639
  54. Schuchman E, Desnick R. Niemann-Pick disease types A and B: acid sphingomyelinase deficiencies. In:  Scriver C,  Beaudet A,  Sly W,  Valle D editor. The metabolic and molecular basis of inherited disease. New York: McGraw-Hill; 1995;p. 2601–2604
  55. Gillis S, Hyam E, Abrahamov A, Elstein D, Zimran A. Platelet function abnormalities in Gaucher disease patients. Am J Hematol. 1999;61:103–106
  56. Hermann G, Pastores GM, Abdelwahab IF, Lorberboym AM. Gaucher disease: assessment of skeletal involvement and therapeutic responses to enzyme replacement. Skeletal Radiol. 1997;26:687–696
  57. Pastores GM, Wallenstein S, Desnick RJ, Luckey MM. Bone density in type 1 Gaucher disease. J Bone Miner Res. 1996;11:1801–1807
  58. Lutsky KF, Tejwani NC. Orthopaedic manifestations of Gaucher disease. Bull NYU Hosp Jt Dis. 2007;65:37–42
  59. Mistry PK, Sirrs S, Chan A, Pritzker MR, Duffy TP, Grace ME, et al. Pulmonary hypertension in type 1 Gaucher's disease: genetic and epigenetic determinants of phenotype and response to therapy. Mol Gente Metab. 2002;77:91–98
  60. Starzyk K, Richards S, Yee J, Smith SE, Kingman W. The long-term international safety experience of imiglucerase therapy for Gaucher disease. Mol Genet Metab. 2007;90:157–163
  61. European Medicines Agengy. Zavesca. European Public Assessment Report. Disponível em: www.emea.eu.int/humandocs/Humans/EPAR/zavesca/zavesca.htm. Accessed: Oct. 8, 2006.
  62. Weinreb NJ, Barranger JA, Charrow J, Grabowski GA, Mankin HJ, Mistry P. Guidance on the use of miglustat for treating patients with type 1 Gaucher disease. Am J Hematol. 2005;80:223–229
  63. Kuczmarski RJ, Ogden CL, Guo SS, et al. 2000 CDC Growth Charts for the United States: methods and development. Vital Health Stat. 2002;11:1–190
  64. Damiano AM, Pastores GM, Ware JE. The health-related quality of life of adults with Gaucher's disease receiving enzyme replacement therapy: results from a retrospective study. Qual Life Res. 1998;7:373–386
  65. Masek BJ, Sims KB, Bove CM, Korson MS, Short P, Norman DK. Quality of life assessment in adults with type 1 Gaucher disease. Qual Life Res. 1999;8:263–268
  66. Schmitz J, Poll LW, Dahl SV. Therapy of adult Gaucher disease. Haematologica. 2007;92:148–152
  67. Wenstrup RJ, Kacena KA, Kaplan P, Pastores GM, Prakash-Cheng A, Zimran A, et al. Effect of enzyme replacement therapy with imiglucerase on BMD in type 1 Gaucher disease. J Bone Miner Res. 2007;22:119–126
  68. Charrow J, Dulisse B, Grabowski GA, Weinreb NJ. The effect of enzyme replacement therapy on bone crisis and bone pain in patients with type 1 Gauchewr disease. Clin Genet. 2007;71:205–211
  69. Weinreb N, Barranger J, Packman S, Prakash-Cheng A, Rosenbloom B, Sims K, et al. Imiglucerase (Cerezyme) improves quality of life in patients with skeletal manifestations of Gaucher disease. Clin Genet. 2007;71:576–588
  70. De Fost M, Hollak CEM, Groener JEM, Aerts JMFG, Maas M, Poll LW, et al. Superior effects of high-dose enzyme replacement therapy in type 1 Gaucher disease on bone marrow involvement and chitotriosidase levels: a 2-center retrospective analysis. Blood. 2006;108:830–835
  71. Brady RO, Kanfer JN, Shapiro D. Metabolism of glucocerebrosides. II. Evidence of an enzymatic deficiency in Gaucher's disease. Biochem Biophys Res Commun. 1965;18:221–225
  72. Bembi B, Ciana G, Mengel E, Terk MR, Martini C, Wenstrup RJ. Bone complications in children with Gaucher disease. Br J Radiol. 2002;75(Suppl 1):A37–A44
  73. Kaplan P, Mazur A, Manor O, Charrow J, Esplin J, Gribble TJ, et al. Acceleration of retarded growth in children with Gaucher disease after treatment with alglucerase. J Pediatr. 1996;129:149–153
  74. Drelichman G, Ponce E, Basack N, Freigeiro D, Aversa L, Graciela E, et al. Clinical consequences of interrupting enzyme replacement therapy in children with type 1 Gaucher disease. J Pediatr. 2007;15:197–201
  75. Pastores GM, Winreb NJ, Aerts H, Andria G, Cox TM, Giralt M, et al. Therapeutic goals in the treatment of Gaucher disease. Semin Hematol. 2004;41(Suppl 5):4–14
  76. Rosenthal DI, Doppelt SH, Mankin HJ, Dambrosia JM, Xavier RJ, McKusick KA, et al. Enzyme replacement therapy for Gaucher disease: skeletal responses to macrophage-targeted glucocerebrosidase. Pediatrics. 1995;96:629–637
  77. Kolodny EH. Comunicação Pessoal, 6th International Postgraduate Course on Lysossomal Storage Diseases, Nierstein-Mainz-Germany, June 10-15, 2007.
  78. Grabowski, GA. Comunicação Pessoal, 1o Encontro Brasileiro do GBDDL-Atualização Terapêutica, Rio de Janeiro-RJ-Brasil, 9-11 de Agosto, 2007.
  79. de Fost M, Hollak CE, Groener JE, Aerts JM, Maas M, Poll LW, et al. Superior effects of high-dose enzyme replacement therapy in type 1 Gaucher disease on bone marrow involvement and chitotriosidase levels: a 2-center retrospective analysis. Blood. 2006;108:830–835
  80. Altarescu G, Schiffmann R, Parker CC, Moore DF, Kreps C, Brady RO, et al. Comparative efficacy of dose regimens in enzyme replacement therapy of type I Gaucher disease. Blood Cells Mol Dis. 2000;26:285–290
  81. de Fost M, Aerts JMFG, Groener JEM, Maas M, Akkerman EM, Wiersma MG, et al. Low frequency maintenance therapy with imiglucerase in adult type I Gaucher disease: a prospective randomized controlled trial. Haematologica. 2007;92:215–221
  82. Mota RM, Mankin H. Use of plain radiography to optimize skeletal outcomes in children with type 1 Gaucher disease in Brazil. J Pediatr Orthop. 2007;27:347–350
  83. Czartoryska B, Tylki-Szymanska A, Lugowska A. Changes in serum chitotriosidase activity with cessation of replacement enzyme (cerebrosidase) administration in Gaucher disease. Clin Biochem. 2000;33:147–149
  84. Maas M, Hangartner T, Mariani G, McHugh K, Moore S, Grabowski GA, et al. Recommendations for the assessment and monitoring of skeletal manifestations in children with Guacher disease. Skeletal Radiol. 2008;37:185–188

 Please see the Author Disclosures at the end of this article.

PII: S0022-3476(09)00674-X

doi: 10.1016/j.jpeds.2009.07.004

The Journal of Pediatrics
Volume 155, Issue 4, Supplement , Pages S10-S18 , October 2009