Medscape is available in 5 Language Editions – Choose your Edition here.


Gaucher Disease Workup

  • Author: Ellen Sidransky, MD; Chief Editor: Maria Descartes, MD  more...
Updated: Nov 24, 2014

Laboratory Studies

Enzyme activity testing

Diagnosis can be confirmed through measurement of glucocerebrosidase activity in peripheral blood leukocytes. A finding of less than 15% of mean normal activity is diagnostic. Heterozygotes generally have half-normal enzyme activity, but as much as 20% overlap with activity levels of healthy controls has been reported, rendering enzymatic testing for carrier status unreliable.

Genotype testing

Molecular diagnosis can be helpful, especially in Ashkenazi patients, in whom 6 GBA1 mutations (ie, N370S, c.84insG, L444P, IVS2+1g>a, V394L, and R496H) account for most disease alleles. In other ethnicities, sequencing of the exons of GBA1 is necessary in order to accurately establish the genotype. Mutation analysis has some, albeit limited, predictive value with respect to disease progression. Caution should be taken in relying solely on PCR-based test results for individual mutations because they cannot reveal the presence of recombinant alleles associated with greater disease severity.

CBC count

Obtain CBC count and differential to assess the degree of cytopenia.

Liver function enzyme testing

Minor elevations of liver enzyme levels are common, even in patients who are mildly affected with Gaucher disease; however, the presence of jaundice or impaired hepatocellular synthetic function merits a full hepatic evaluation. Coagulations studies should be monitored.

Associated marker testing

Angiotensin-converting enzyme levels are typically elevated, as are total acid phosphatase and ferritin levels. Monitoring levels of another enzyme, chitotriosidase, is also useful in monitoring the disease, except in the 10% of the population who have a deficiency in this protein.


Imaging Studies

Ultrasonography of the abdomen can reveal the extent of organomegaly. MRI is more accurate than ultrasonography in determining organ size. Hip MRI may be useful in revealing early avascular necrosis. MRI may be useful in delineating the degree of marrow infiltration and evaluating spinal involvement. Skeletal radiography can be used to detect and evaluate skeletal manifestations of Gaucher disease. Perform chest radiography to evaluate pulmonary manifestations. Dual-energy x-ray absorptiometry (DEXA) is useful in evaluating osteopenia.


Other Tests

Echocardiograms are helpful in evaluating the possibility of pulmonary hypertension.

In neurononpathic Gaucher disease, EEG, brainstem-evoked potential, swallow studies, and neuro-ophthalmalogic evaluation should be performed at regular intervals.



Bone marrow aspiration

In the past, the diagnosis was confirmed with the finding of classic glycolipid-laden macrophages in bone marrow aspirate collected because of hematological abnormalities; however, aspiration is not a recommended diagnostic tool. Similar pseudo-Gaucher cells have also been described in individuals with other disorders, including chronic granulocytic leukemia, thalassemia, multiple myeloma, Hodgkin disease, plasmacytoid lymphomas, acquired immunodeficiency syndrome (AIDS), and Mycobacterium avium– intracellulare infection.

Bone marrow aspiration should not be the initial diagnostic test because the blood enzyme test is sensitive, specific, and much less invasive.

Liver biopsy

Liver biopsy is occasionally performed to assess unexplained hepatomegaly. It can be avoided in most patients when the diagnosis is suspected because a specific diagnostic test is available.


Histologic Findings

In Gaucher disease, classic glycolipid-laden macrophages are found in bone marrow aspirate or in liver biopsy samples. On liver biopsy samples, glycolipid-laden Gaucher cells are evident in the sinusoids, but the hepatocytes do not manifest overt glycolipid storage, presumably because of biliary excretion of glucocerebroside and because exogenous glycolipid turnover is handled by the mononuclear phagocytes. The sparing of hepatocytes is consistent with the low incidence of liver failure in individuals with Gaucher disease.

The pathologic hallmark of Gaucher disease is the presence of Gaucher cells in the macrophage-monocyte system, particularly in the bone marrow. These cells, which are 20-100 mm in diameter, have a characteristic wrinkled-paper appearance, resulting from intracytoplasmic substrate deposition, and stain strongly positive with periodic acid–Schiff. Histologic evaluation of biopsy specimens should not be used as a first-line diagnostic tool.

Contributor Information and Disclosures

Ellen Sidransky, MD Senior Investigator, Chief, Section on Molecular Neurogenetics, Medical Genetics Branch, National Human Genome Research Institute, NIH

Ellen Sidransky, MD is a member of the following medical societies: American Society of Human Genetics, International Parkinson and Movement Disorder Society, Society for Pediatric Research, Society for Inherited Metabolic Disorders

Disclosure: Nothing to disclose.

Specialty Editor Board

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

Chief Editor

Maria Descartes, MD Professor, Department of Human Genetics and Department of Pediatrics, University of Alabama at Birmingham School of Medicine

Maria Descartes, MD is a member of the following medical societies: American Academy of Pediatrics, American College of Medical Genetics and Genomics, American Medical Association, American Society of Human Genetics, Society for Inherited Metabolic Disorders, International Skeletal Dysplasia Society, Southeastern Regional Genetics Group

Disclosure: Nothing to disclose.

Additional Contributors

Robert D Steiner, MD Chief Medical Officer, Acer Therapeutics; Clinical Professor, University of Wisconsin School of Medicine and Public Health

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 and Genomics, American Society of Human Genetics, Society for Inherited Metabolic Disorders, Society for Pediatric Research, Society for the Study of Inborn Errors of Metabolism

Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: Acer Therapeutics; Retrophin; Raptor Pharma; Veritas Genetics; Censa Pharma<br/>Received income in an amount equal to or greater than $250 from: Acer Therapeutics; Retrophin; Raptor Pharma; Censa Pharma.


The author acknosledges the assistance of Mary E. LaMarca, who co-authored the initial version of this chapter prior to her death in 2010.

  1. Harrison L. Evidence Mounting for Eliglustat in Gaucher's Disease. Medscape Medical News. Available at Accessed: November 10, 2014.

  2. Vitner EB, Farfel-Becker T, Eilam R, Biton I, Futerman AH. Contribution of brain inflammation to neuronal cell death in neuronopathic forms of Gaucher's disease. Brain. 2012 Jun. 135(Pt 6):1724-35. [Medline].

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

  4. Sidransky E, Nalls MA, Aasly JO, Aharon-Peretz J, Annesi G, Barbosa ER. Multicenter analysis of glucocerebrosidase mutations in Parkinson's disease. N Engl J Med. 2009 Oct 22. 361(17):1651-61. [Medline]. [Full Text].

  5. Siebert M, Sidransky E, Westbroek W. Glucocerebrosidase is shaking up the synucleinopathies. Brain. 2014 May. 137:1304-22. [Medline]. [Full Text].

  6. Nalls MA, Duran R, Lopez G, Kurzawa-Akanbi M, McKeith IG, Chinnery PF, et al. A multicenter study of glucocerebrosidase mutations in dementia with Lewy bodies. JAMA Neurol. 2013 Jun. 70(6):727-35. [Medline]. [Full Text].

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

  8. Cerdelga (eliglustat) prescribing information. [package insert]. IDA Industrial Park, Old Kilmeaden Road, Waterford, Ireland: Genzyme Ireland, Ltd. August 2014.

  9. Lowes, R. Medscape Medical News. FDA Clears Eliglustat (Cerdelga) for Gaucher Disease. Available at

  10. Zimran A, Altarescu G, Phillips M, Attias D, Jmoudiak M, Deeb M. Phase I/II and extension study of velaglucerase alfa (Gene-ActivatedTM human glucocerebrosidase) replacement therapy in adults with type 1 Gaucher disease: 48-month experience. Blood. 2010 Mar 18. [Medline].

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

  12. Hollak CE. An evidence-based review of the potential benefits of taliglucerase alfa in the treatment of patients with Gaucher disease. Core Evid. 2012. 7:15-20. [Medline]. [Full Text].

  13. 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. 2008 Dec. 122(6):1182-90. [Medline].

  14. Westbroek W, Gustafson AM, Sidransky E. Exploring the link between glucocerebrosidase mutations and parkinsonism. Trends Mol Med. 2011 Sep. 17(9):485-93. [Medline]. [Full Text].

  15. Hruska KS, LaMarca ME, Scott CR, Sidransky E. Gaucher disease: mutation and polymorphism spectrum in the glucocerebrosidase gene (GBA). Hum Mutat. 2008 May. 29(5):567-83. [Medline].

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

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

  18. AH Futerman and A Zimran. Gaucher Disease. Boca Raton, FL: CRC Press; 2006.

  19. 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].

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

  21. 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. 1991 May 23. 324(21):1464-70. [Medline].

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

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

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

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

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

  27. 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].

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

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

  30. 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. 2003 Aug. 143(2):273-6. [Medline].

  31. 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. 2009 Feb. 11(2):92-100. [Medline].

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

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

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

  35. 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. 2000 Jun. 66(6):1777-86. [Medline]. [Full Text].

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

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

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

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

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

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

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

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

  44. 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].

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

  46. 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. 2003 Mar. 72(3):519-34. [Medline].

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

  48. 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].

  49. Zimran A. How I treat Gaucher disease. Blood. 2011 Aug 11. 118(6):1463-71. [Medline].

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

Autosomal recessive inheritance pattern.
All material on this website is protected by copyright, Copyright © 1994-2016 by WebMD LLC. This website also contains material copyrighted by 3rd parties.