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

Gaucher Disease: Differential Diagnoses & Workup

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

Differential Diagnoses

Niemann-Pick Disease

Other Problems to Be Considered

Multiple myeloma

Workup

Laboratory Studies

The following studies are indicated in Gaucher disease:

  • 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 GBA mutations (ie, N370S, c.84insG, L444P, IVS2+1g>a, V394L, and R496H) account for most disease alleles. 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: Ultrasonography of the abdomen can reveal the extent of organomegaly.
  • MRI
    • 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.
  • Radiography
    • 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 scanning: Dual-energy x-ray absorptiometry (DEXA) is useful in evaluating osteopenia.

Procedures

  • 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 m m 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.

More on Gaucher Disease

Overview: Gaucher Disease
Differential Diagnoses & Workup: Gaucher Disease
Treatment & Medication: Gaucher Disease
Follow-up: Gaucher Disease
Multimedia: Gaucher Disease
References
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Further Reading

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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

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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.

 
 
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