Gaucher disease type 1 is by far the most prevalent form of the disorder (approximately 95% of cases)* and is thus the presentation most likely to be encountered by physicians.1,2
It can be difficult to recognise Gaucher disease because of its rarity and because typical signs and symptoms are common to a number of conditions.3 In a 2005 international survey, only 20% of haematologists-oncologists considered Gaucher disease in the differential diagnosis of a hypothetical patient presenting with all the classical signs and symptoms of Gaucher disease type 1.4
Common presenting signs and symptoms of Gaucher disease include easy bruising or bleeding, enlarged abdomen due to splenomegaly and/or hepatomegaly, fatigue, bone and joint pain and/or bone fractures, and delayed growth.4 There is wide variability in the age of onset and the severity and combination of manifestations, even within Gaucher disease subtypes.5
Prompt recognition and diagnosis of Gaucher disease is important because the majority of patients can be treated with disease-specific therapies. Patients with Gaucher disease have been misdiagnosed with leukaemia, immune thrombocytopenic purpura, autoimmune disease, hepatic cirrhosis, idiopathic avascular necrosis, viral disease, idiopathic splenomegaly, and anaemia of chronic disease. Misdiagnosis can lead to complications and inappropriate medical procedures.6
When to suspect Gaucher disease
Gaucher disease may be suspected in any patient with unexplained splenomegaly and/or thrombocytopenia.6 Splenomegaly and/or thrombocytopenia are early manifestations of all types of Gaucher disease that are present in the majority of patients at diagnosis** (see more in Information for Haematologists). Suspicion is heightened in patients of Ashkenazi Jewish descent (see more in Diagnostic algorithms).6,7 It should be noted that absence of splenomegaly does not rule out Gaucher disease.
Histological identification of Gaucher disease
It is not uncommon for Gaucher disease to be identified serendipitously as a result of histological findings on tissue biopsy specimens (principally bone marrow or liver). Tissue biopsy may be performed during investigations for cytopenias or visceromegaly, usually before Gaucher disease is considered.6,7 Glucosylceramide-laden tissue macrophages have a characteristic appearance in specimens from individuals with Gaucher disease. Known as “Gaucher cells”, they have been described as signet rings with “wrinkled tissue paper” due to the nucleus being pushed to the periphery by lysosomes storing glucosylceramide.5
Image courtesy of Peter Maslak ASH Image Bank 2009 doi:10.1182/ashimagebank-2009-9-00094.
True Gaucher cells are unique to Gaucher disease. However, macrophages with a similar appearance (pseudo-Gaucher cells) have been found in other conditions including multiple myeloma, myelodysplasia and myelodysplastic syndromes, chronic myeloid leukaemia, pulmonary tuberculosis, mycobacterioses, and sickle cell disease.6 Because Gaucher cells and pseudo-Gaucher cells are not easily distinguishable and less invasive, more robust diagnostic tests are available. Tissue biopsy should not be performed to diagnose Gaucher disease. Rather, a serendipitous finding of Gaucher cells should prompt confirmative diagnostic testing (see more in Testing and Diagnosis).7
Radiological identification of Gaucher disease
Gaucher disease is sometimes identified among patients undergoing radiological investigations. Bone findings suggestive of Gaucher disease include undertubulation of the distal femur (Erlenmeyer flask deformity) and endosteal scalloping as a sign of bone marrow infiltration, both visible with conventional radiograghy.7,8 These findings should raise suspicion of Gaucher disease and prompt confirmative diagnostic testing.
It should be noted that radiographic evidence of bone involvement in Gaucher disease may be present in the absence of symptoms of bone pain. Furthermore, patients may have severe bone disease in the absence of significant haematologic manifestations.9
Erlenmeyer flask deformity
Image courtesy of www.radrounds.com
Special considerations for Gaucher disease type 2
Prompt and accurate diagnosis of this severe subtype is important for providing appropriate supportive care and assisting affected families with family planning and genetic counselling.10 Current disease-specific treatments are not indicated for Gaucher disease type 2.
Clinical signs of Gaucher disease type 2 usually appear in infancy but may be present prenatally or in neonates. Because Gaucher disease type 2 is exceptionally rare (1:100,000 to 1:500,000 live births) and displays phenotypic heterogeneity, it can be challenging to recognise.10,11 Hepatosplenomegaly, haematological abnormalities, developmental delay, and retroflexion of the neck should raise suspicion of Gaucher disease type 2.10,12 Affected infants often fail to thrive due to a combination of anorexia, nausea, hypotonia or hypertonia, vomiting and feeding difficulties.10 Brainstem abnormalities are prominent, including a convergent squint, ocular paresis, trismus, and dysphagia.12
It can be difficult to differentiate Gaucher disease type 2 and type 3 in first 6-9 months of life.13 However, it is important that the correct subtype is identified because of the impact on treatment decisions.
*In North American, European and other “European-derived” Caucasian populations. **"At diagnosis" is defined as the data point closest to the diagnosis date but no more than ± 2 years from diagnosis.