eMedicine Specialties > Pediatrics: Genetics and Metabolic Disease > Metabolic Diseases

Gaucher Disease: Follow-up

Author: Ellen Sidransky, MD, Senior Investigator, Consulting Staff, Chief, Section on Molecular Neurogenetics, Clinical Neuroscience Branch, National Institute of Mental Health; Senior Investigator, Acting Chief, Medical Genetics Branch, National Human Genome Research Institute
Contributor Information and Disclosures

Updated: Oct 16, 2009

Follow-up

Further Inpatient Care

  • Patients with Gaucher disease who have bone crises may require admission for pain relief.
  • Patients with severe hematologic manifestations may have episodes of bleeding that require inpatient treatment.

Further Outpatient Care

  • Most symptomatic patients with Gaucher disease receive enzyme replacement therapy (ERT), which is provided on an outpatient basis.3 Monitoring for allergic reactions is essential.
  • Monitoring patients who receive miglustat (Zavesca) every 6 months for possible development of peripheral neuropathy is recommended.
  • Patients with osteoporosis have responded favorably to bisphosphonates.

Deterrence/Prevention

  • Gaucher disease is inherited as an autosomal recessive trait. Although it is panethnic, Gaucher disease is more common in individuals of Ashkenazi Jewish. Although carrier-screening programs in this population have been established at some centers to identify couples at risk for having a child affected with Gaucher disease, testing must be offered in conjunction with genetic counseling to provide couples at risk, even asymptomatic individuals, with a description of the range of associated phenotypes and their options, which include prenatal diagnosis.

Complications

  • Bone crises may occur secondarily to infarcts. Avascular necrosis of the hip is not uncommon.
  • Splenic rupture can result from trauma.
  • Cirrhosis is a rare complication.
  • Rarely, pulmonary infiltration by Gaucher cells may manifest as overt lung disease, which may present as pulmonary infiltrates and lung consolidation; this pattern is especially common in patients with type 2 disease.
  • Parenchymal infiltration with fibrosis has been described in children with type 3 disease.
  • Intrapulmonary vascular dilatation in the presence or absence of portal hypertension has also been described in some patients with Gaucher disease, resulting in hypoxic lung disease.
  • Adult patients with pulmonary hypertension in the absence of infiltrative disease have been described; these patients may follow an inexorable progressive course despite therapy.
  • Hematologic abnormalities, including anemia, thrombocytopenia, and leukopenia, are common in individuals with Gaucher disease
  • Immunologic abnormalities, including hypergammaglobulinemia, T-lymphocyte deficiency in the spleen, and impaired neutrophil chemotaxis, are also common. The malignancy multiple myeloma is more common in individuals with Gaucher disease.
  • New evidence suggests that mutations in the gene for glucocerebrosidase may be a risk factor for the development of Parkinson disease.4

Prognosis

  • Many individuals with Gaucher disease have few manifestations and a normal life expectancy without any intervention.
  • The prognosis for symptomatic patients with type 1 or type 3 Gaucher disease who receive treatment is very good, with a decrease in organomegaly and an eventual rise in hemoglobin levels and platelet counts.
  • A recent study estimated life expectancy at birth in patients with type 1 Gaucher disease to be 68 years, compared with 77 years in the reference population.5
  • Skeletal disease is slow to respond to ERT and widely varies.
  • Some patients describe symptomatic improvement within the first year of treatment, although a much longer period of ERT is required to achieve a radiologic response.

Patient Education

  • Patients with Gaucher disease and their families require education regarding the disease manifestations, variability in symptoms and disease progression, and potential complications. In addition, they should be counseled regarding the genetic risks

Miscellaneous

Medicolegal Pitfalls

  • Discussion of the genetic etiology and autosomal recessive pattern of inheritance of Gaucher disease with patients and their families is imperative. Full genetic counseling should be offered.

Special Concerns

  • Women with Gaucher disease have had successful pregnancies.6 Some patients have received treatment during pregnancy without complications. In patients who are not undergoing treatment, hematologic status should be monitored.
 


More on Gaucher Disease

Overview: Gaucher Disease
Differential Diagnoses & Workup: Gaucher Disease
Treatment & Medication: Gaucher Disease
Follow-up: Gaucher Disease
Multimedia: Gaucher Disease
References
[ CLOSE WINDOW ]

References

  1. Grabowski GA. Phenotype, diagnosis, and treatment of Gaucher's disease. Lancet. Oct 4 2008;372(9645):1263-71. [Medline].

  2. Sidransky E, Pastores GM, Mori M. Dosing enzyme replacement therapy for Gaucher disease: older, but are we wiser?. Genet Med. Feb 2009;11(2):90-1. [Medline].

  3. Andersson H, Kaplan P, Kacena K, Yee J. Eight-year clinical outcomes of long-term enzyme replacement therapy for 884 children with Gaucher disease type 1. Pediatrics. Dec 2008;122(6):1182-90. [Medline].

  4. Mitsui J, Mizuta I, Toyoda A, Ashida R, et al. Mutations for Gaucher disease confer high susceptibility to Parkinson disease. Arch Neurol. May 2009;66(5):571-6. [Medline].

  5. Weinreb NJ, Deegan P, Kacena KA, Mistry P, Pastores GM, Velentgas P, et al. Life expectancy in Gaucher disease type 1. Am J Hematol. Dec 2008;83(12):896-900. [Medline].

  6. Mamopoulos AM, Hughes DA, Tuck SM, Mehta AB. Gaucher disease and pregnancy. J Obstet Gynaecol. Apr 2009;29(3):240-2. [Medline].

  7. Amato D, Stachiw T, Clarke JT, Rivard GE. Gaucher disease: variability in phenotype among siblings. J Inherit Metab Dis. 2004;27(5):659-69. [Medline].

  8. Andersson HC, Charrow J, Kaplan P, et al. Individualization of long-term enzyme replacement therapy for Gaucher disease. Genet Med. Feb 2005;7(2):105-10. [Medline].

  9. Barton NW, Brady RO, Dambrosia JM, et al. Replacement therapy for inherited enzyme deficiency--macrophage-targeted glucocerebrosidase for Gaucher's disease. N Engl J Med. May 23 1991;324(21):1464-70. [Medline].

  10. Beutler E. Lysosomal storage diseases: natural history and ethical and economic aspects. Mol Genet Metab. Jul 2006;88(3):208-15. [Medline].

  11. Beutler E, Gelbart T, Scott CR. Hematologically important mutations: Gaucher disease. Blood Cells Mol Dis. Nov-Dec 2005;35(3):355-64. [Medline].

  12. Beutler E, Grabowski GA, CR Scriver, et al Eds. The Metabolic and Molecular Bases of Inherited Disease. McGraw-Hill, New York. 2001;3635-68.

  13. Bohlega S, Kambouris M, Shahid M, et al. Gaucher disease with oculomotor apraxia and cardiovascular calcification (Gaucher type IIIC). Neurology. Jan 11 2000;54(1):261-3. [Medline].

  14. Charrow J, Andersson HC, Kaplan P, et al. Enzyme replacement therapy and monitoring for children with type 1 Gaucher disease: consensus recommendations. J Pediatr. Jan 2004;144(1):112-20. [Medline].

  15. Cox TM, Aerts JM, Andria G, et al. The role of the iminosugar N-butyldeoxynojirimycin (miglustat) in the management of type I (non-neuronopathic) Gaucher disease: a position statement. J Inherit Metab Dis. 2003;26(6):513-26. [Medline].

  16. Depaolo J, Goker-Alpan O, Samaddar T, Lopez G, Sidransky E. The association between mutations in the lysosomal protein glucocerebrosidase and parkinsonism. Mov Disord. May 7 2009;[Medline].

  17. Futerman AH, Zimran A. Gaucher Disease. CRC Press, Boca Raton, FL. 2006.

  18. Goker-Alpan O, Schiffmann R, Park JK, et al. Phenotypic continuum in neuronopathic Gaucher disease: an intermediate phenotype between type 2 and type 3. J Pediatr. Aug 2003;143(2):273-6. [Medline].

  19. Grabowski GA, Kacena K, Cole JA, et al. Dose-response relationships for enzyme replacement therapy with imiglucerase/alglucerase in patients with Gaucher disease type 1. Genet Med. Feb 2009;11(2):92-100. [Medline].

  20. Grabowski GA, Leslie N, Wenstrup R. Enzyme therapy for Gaucher disease: the first 5 years. Blood Rev. Jun 1998;12(2):115-33. [Medline].

  21. Itzchaki M, Lebel E, Dweck A, et al. Orthopedic considerations in Gaucher disease since the advent of enzyme replacement therapy. Acta Orthop Scand. Dec 2004;75(6):641-53. [Medline].

  22. Jmoudiak M, Futerman AH. Gaucher disease: pathological mechanisms and modern management. Br J Haematol. Apr 2005;129(2):178-88. [Medline].

  23. Koprivica V, Stone DL, Park JK, et al. Analysis and classification of 304 mutant alleles in patients with type 1 and type 3 Gaucher disease. Am J Hum Genet. Jun 2000;66(6):1777-86. [Medline]. [Full Text].

  24. [Guideline] Langlois S, Wilson RD. Carrier screening for genetic disorders in individuals of Ashkenazi Jewish descent. J Obstet Gynaecol Can. Apr 2006;28(4):324-43. [Medline].

  25. Lwin A, Orvisky E, Goker-Alpan O, et al. Glucocerebrosidase mutations in subjects with parkinsonism. Mol Genet Metab. Jan 2004;81(1):70-3. [Medline].

  26. Mistry PK, Abrahamov A. A practical approach to diagnosis and management of Gaucher's disease. Baillieres Clin Haematol. Dec 1997;10(4):817-38. [Medline].

  27. NIH Technology Assessment Panel on Gaucher Disease. Gaucher disease. Current issues in diagnosis and treatment. JAMA. Feb 21 1996;275(7):548-53. [Medline].

  28. Park JK, Orvisky E, Tayebi N, et al. Myoclonic epilepsy in Gaucher disease: genotype-phenotype insights from a rare patient subgroup. Pediatr Res. Mar 2003;53(3):387-95. [Medline].

  29. Sibille A, Eng CM, Kim SJ, et al. Phenotype/genotype correlations in Gaucher disease type I: clinical and therapeutic implications. Am J Hum Genet. Jun 1993;52(6):1094-101. [Medline]. [Full Text].

  30. Sidransky E. Gaucher disease: complexity in a "simple" disorder. Mol Genet Metab. Sep-Oct 2004;83(1-2):6-15. [Medline].

  31. Svennerholm L, Erikson A, Groth CG, et al. Norrbottnian type of Gaucher disease--clinical, biochemical and molecular biology aspects: successful treatment with bone marrow transplantation. Dev Neurosci. 1991;13(4-5):345-51. [Medline].

  32. Tayebi N, Stone DL, Sidransky E. Type 2 gaucher disease: an expanding phenotype. Mol Genet Metab. Oct 1999;68(2):209-19. [Medline].

  33. Tayebi N, Stubblefield BK, Park JK, et al. Reciprocal and nonreciprocal recombination at the glucocerebrosidase gene region: implications for complexity in Gaucher disease. Am J Hum Genet. Mar 2003;72(3):519-34. [Medline].

  34. Weinreb NJ, Aggio MC, Andersson HC, et al. Gaucher disease type 1: revised recommendations on evaluations and monitoring for adult patients. Semin Hematol. Oct 2004;41(4 Suppl 5):15-22. [Medline].

  35. Wenstrup RJ, Roca-Espiau M, Weinreb NJ, Bembi B. Skeletal aspects of Gaucher disease: a review. Br J Radiol. 2002;75 Suppl 1:A2-12. [Medline]. [Full Text].

  36. Zimran A, Altarescu G, Rudensky B, et al. Survey of hematological aspects of Gaucher disease. Hematology. Apr 2005;10(2):151-6. [Medline].

[ CLOSE WINDOW ]

Further Reading

[ CLOSE WINDOW ]

Keywords

Gaucher disease, Gaucher’s disease, glucocerebrosidase deficiency, cerebroside lipidosis, acid beta-glucosidase deficiency, splenomegaly, anemia, lipid storage disease, lysosomal storage disease, glucocerebrosidase, glucosylceramidase, GBA, pancytopenia, massive hepatosplenomegaly, diffuse infiltrative pulmonary disease, parkinsonism, Lewy body

[ CLOSE WINDOW ]

Contributor Information and Disclosures

Author

Ellen Sidransky, MD, Senior Investigator, Consulting Staff, Chief, Section on Molecular Neurogenetics, Clinical Neuroscience Branch, National Institute of Mental Health; Senior Investigator, Acting Chief, Medical Genetics Branch, National Human Genome Research Institute
Ellen Sidransky, MD is a member of the following medical societies: American Society of Human Genetics, Society for Inherited Metabolic Disorders, and Society for Pediatric Research
Disclosure: Nothing to disclose.

Medical Editor

Robert D Steiner, MD, Professor, Departments of Pediatrics and Molecular and Medical Genetics, Vice Chair for Research, Department of Pediatrics, Oregon Health & Science University; Director and Consulting Staff, Metabolic Bone Disease Clinic, Shriner's Hospital and Doernbecher Children's Hospital; Co-Director: Pediatric and Child Health Research, Oregon Clinical and Translational Research Institute (CTSA).
Robert D Steiner, MD is a member of the following medical societies: American Academy of Pediatrics, American Association for the Advancement of Science, American College of Medical Genetics, American Society of Human Genetics, Oregon Medical Association, Society for Inherited Metabolic Disorders, Society for Pediatric Research, Society for the Study of Inborn Errors of Metabolism, and Western Society for Pediatric Research
Disclosure: Genzyme Honoraria Speaking and teaching; Genzyme Grant/research funds Other; Shire Honoraria Speaking and teaching; Actelion Honoraria Speaking and teaching; Biomarin Honoraria Speaking and teaching; Biomarin Consulting fee Consulting; Amicus  Consulting

Pharmacy Editor

Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine
Disclosure: Pfizer Inc Stock Investment from financial planner; Avanir Pharma Stock Investment from financial planner ; WebMD Salary and stock Employment and investment from financial planner

Managing Editor

Hagop Youssoufian, MD, MSc, Vice President of Clinical Research, ImClone Systems Incorporated
Hagop Youssoufian, MD, MSc is a member of the following medical societies: American Society for Clinical Investigation, American Society of Clinical Oncology, American Society of Hematology, and American Society of Human Genetics
Disclosure: Nothing to disclose.

CME Editor

Paul D Petry, DO, FACOP, FAAP, Consulting Staff, Freeman Pediatric Care, Freeman Health System
Paul D Petry, DO, FACOP, FAAP is a member of the following medical societies: American Academy of Osteopathy, American Academy of Pediatrics, American College of Osteopathic Pediatricians, and American Osteopathic Association
Disclosure: Nothing to disclose.

Chief Editor

Bruce Buehler, MD, Professor, Department of Pediatrics, Pathology and Microbiology, Executive Director, Hattie B Munroe Center for Human Genetics, University of Nebraska Medical Center
Bruce Buehler, MD is a member of the following medical societies: American Academy for Cerebral Palsy and Developmental Medicine, American Academy of Pediatrics, American Association on Mental Retardation, American College of Medical Genetics, American College of Physician Executives, American Medical Association, and Nebraska Medical Association
Disclosure: Nothing to disclose.

 
 
HONcode

We subscribe to the
HONcode principles of the
Health On the Net Foundation

All material on this website is protected by copyright, Copyright© 1994- by Medscape.
This website also contains material copyrighted by 3rd parties.

DISCLAIMER: The content of this Website is not influenced by sponsors. The site is designed primarily for use by qualified physicians and other medical professionals. The information contained herein should NOT be used as a substitute for the advice of an appropriately qualified and licensed physician or other health care provider. The information provided here is for educational and informational purposes only. In no way should it be considered as offering medical advice. Please check with a physician if you suspect you are ill.