To view this page ensure that Adobe Flash Player version 11.1.0 or greater is installed.
Metabolic Disorders Gaucher Disease
A Rare Condition in Haematological Practice – Gaucher Disease
Centro Anemie Congenite, Ospedale Maggiore Policlinico IRCCS, University of Milan, Italy
Abstract Gaucher disease, which is caused by an inherited glucocerebrosidase deficiency, is the most prevalent lysosomal storage disease
worldwide. Estimated prevalence of Gaucher disease is 1:50,000 in most countries and the disease has its highest incidence in the
Ashkenazi Jewish population. Type 1 (non-neuropathic) Gaucher disease is by far the most common form. Gaucher disease type 1
should be considered in cases of unexplained splenomegaly with or without bleeding diathesis, skeletal manifestations or hepatomegaly.
Diagnosis is made by demonstrating decreased glucocerebrosidase activity in peripheral blood leucocytes. Dried blood spots can be
used for screening but conventional enzyme assay on heparinised blood is essential. Patients with Gaucher disease may have extensive
organ involvement despite relatively minor overt symptomatology. Evidence suggests that Gaucher disease may remain undiagnosed for
years, leading to severe complications that are preventable or reversible with enzyme replacement therapy. These complications include
avascular necrosis, severe bleeding, chronic bone pain, pathological fractures, growth failure, liver pathology and life-threatening sepsis.
Most patients with Gaucher disease are initially evaluated by a haematologist–oncologist. Improved education is needed to enable prompt
detection of Gaucher disease. An increased risk of multiple myeloma and haematological and non-haematological malignancies has been
reported in type 1 Gaucher disease. This review aims to offer familiarisation with a rare disorder in haematological practice, focusing on
adult patient management.
Keywords Gaucher disease, glucocerebrosidase, cancer, haematological malignancy, multiple myeloma, monoclonal gammopathy of undermined
significance (MGUS), diagnosis, splenomegaly, thrombocytopenia
Disclosure: Maria-Domenica Cappellini has the following conflicts of interest to declare: Sanofi/Genzyme advisory board, Novartis advisory board.
Acknowledgements: Editorial assistance was provided by Catherine Amey at Touch Medical Media, London, UK, funded by Genzyme, a Sanofi Company.
Open Access: This article is published under the Creative Commons Attribution Noncommercial License, which permits any non-commercial use, distribution, adaptation
and reproduction provided the original author(s) and source are given appropriate credit.
Received: 23 April 2015 Accepted: 13 May 2015 Citation: European Oncology & Haematology, 2015;11(1):15–20
Correspondence: Maria-Domenica Cappellini, Centro Anemie Congenite, Ospedale Maggiore Policlinico IRCCS, University of Milan, Italy. E: email@example.com
Support: The publication of this article was supported by Genzyme, a Sanofi Company. Genzyme were given the opportunity to review the article for scientific accuracy
before submission. Any resulting changes were made at the author’s discretion.
Gaucher disease (OMIM #230800) is an inherited deficiency of lysosomal
enzyme acid ß-glucosidase (glucocerbrosidase, GBA1; EC 22.214.171.124) due
to mutations in the glucocerebrosidase gene, GBA1. 1 Genetic mutations
affect the enzyme’s catalytic function, intracellular stability or subcellular
trafficking. 2–4 Such enzyme deficiency results in the accumulation of
glucocerebroside in lysosomes of macrophages (known as Gaucher
cells, Figure 1), which are observed in many organs, primarily in the
bone marrow, liver, spleen and lymph node parenchyma. The finding
of an association between the GBA mutation in the heterozygous state
and Parkinson’s disease indicates that there may be pathogenic roles for
GBA mutations beyond enzyme deficiency. 5–7
Gaucher cells are typically 20–100 µm in diameter with eccentrically
placed nuclei and cytoplasm with characteristic crinkles and striations. 8–10
However, untreated patients with type 1 Gaucher disease have recently
been shown to display a considerable proportion of Gaucher cells with
atypical cytomorphology. 11
The glucocerebroside concentration in spleens can be increased
10 to 1,000-fold, but high levels may also be present in the bone
Tou ch ME dical ME d ia
marrow and liver. 12 Glucosylceramide accumulation leads to variable
combinations of: 13
• Splenomegaly with abdominal discomfort, often the presenting
symptom of Gaucher disease. 14
• Anaemia with chronic fatigue. 15
• Spontaneous bruising and bleeding – due to thrombocytopenia
and/or Gaucher disease-associated coagulopathy. 16 This is initially
a result of enhanced blood cell clearance by the enlarged spleen.
At a later disease stage, or in patients who have undergone a
splenectomy, replacement of the bone marrow by Gaucher cells
adds to cytopenia development.
• Hepatomegaly and abnormal liver function.
• Diverse bone disease manifestations, including chronic bone
pain, acute bone crises, defective bone mineralisation, infarction,
osteonecrosis, osteolysis and pathological fractures. 17 Skeletal
disease affects more than 80 % of patients with Gaucher disease and
can have a major impact on patient quality of life. 18,19
• Impaired neutrophil function and neutropenia may cause an
increased susceptibility to infection. 20