Gaucher Disease Workup

Updated: Oct 05, 2023
  • Author: Ellen Sidransky, MD; Chief Editor: Maria Descartes, MD  more...
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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 around 90% of disease alleles. However, these variants only account for 50-75% in other ethnicities, and therefore 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 always identify  the presence of recombinant alleles associated with greater disease severity. A complete analysis of the GBA1 gene is especially important in situations where either biomarkera or disease phenotype is at odds with enzymatic activity and further disease characterization is necessary for definitive diagnosis, genetic counseling or family planning. [17]

CBC count

A CBC count with a platelet count and differential should be performed 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 typically are elevated, as are total acid phosphatase and ferritin levels. These levels may normalize or may remain elevated with treatment. 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.

In recent years levels of glucosylsphingosine, a downstream metabolic product of glucosylceramide, have been shown to be a useful disease biomarker, as it correlates with disease severity and with response to therapy. [18]


Imaging Studies

Ultrasonography of the abdomen can reveal the extent of organomegaly, and can be useful especially in young children. MRI is more accurate than ultrasonography in determining organ size and is used for volumetric assessment. MRI may be useful in revealing early skeletal involvement, such as avascular necrosis and spinal degradation, as well as in delineating the degree of bone marrow infiltration. Skeletal radiography can be used to detect and evaluate skeletal manifestations of Gaucher disease. Chest radiography should be performed to evaluate pulmonary manifestations. Dual-energy x-ray absorptiometry (DEXA) is useful in evaluating osteopenia. Bone scans may be useful in diagnosing bone crises.


Other Tests

Echocardiograms are helpful in evaluating the possibility of pulmonary hypertension.

In neuronopathic Gaucher disease, depending on phenotypic presentation, EEG, brainstem-evoked potential, swallow studies, and neuro-ophthalmologic 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 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– intracellular infection.

Bone marrow aspiration should not be the initial diagnostic test because the blood enzyme test is sensitive, specific, and much less invasive; in fact, such biopsies rarely are indicated.

Liver biopsy

Liver biopsy occasionally is performed to assess unexplained hepatomegaly. However, it should 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, PAS. Histologic evaluation of biopsy specimens should not be used as a first-line diagnostic tool.