INTRODUCING
Gaucher disease is a rare, inherited metabolic disorder and is classified as a type of lysosomal storage disease known as sphingolipidosis.
Can Gaucher disease be linked to immunological disorders?
Immune system abnormalities observed in patients with Gaucher disease include polyclonal hypergammaglobulinaemia, which is an uncommon condition characterised by elevated levels of immunoglobulins in the blood, monoclonal gammopathy of undetermined significance, and myeloma.1,2 Autoimmune haemolytic anaemia and thrombocytopaenia may also be present in patients with Gaucher disease.3 Data from murine models of Gaucher disease via conditional knockout of the GBA1 gene in haematopoietic cells culminates in considerable, widespread, organ-specific dysfunction in immune cells. Dysregulation of the thymus was noted in these GBA1 knockout mice and was associated with impairments in T-cell maturation, aberrant B-cell recruitment, enhanced antigen presentation and impairments in egress of mature thymocytes. These changes in immune function correlated with disease severity.4
Numerous inflammatory and antigen-presenting cell types have also been implicated in patients with Gaucher disease. It is suggested that macrophage activation induced by excess glucosylceramide initiates the release of monocytes and neutrophils, which attract cytokines and C-C and C-X-C chemokines, and the recruitment of neutrophils to visceral organs. Following the entry of macrophages into visceral organs, they are thought to mature into a number of tissue-specific macrophages and dendritic-cell subsets, leading to an increase in the release of inflammatory markers and the mediation of inflammation.5
One study showed that immune alterations were shown to persist in 31 patients (females, n=23; males, n=8) with Gaucher disease even after long-term therapy had been initiated. Persistent immune alterations, especially in B cells and dendritic cells, correlated with a delay in the initiation of enzyme replacement therapy for patients with Gaucher disease. It was also noted that although enzyme replacement therapy may reverse some of these immune abnormalities, the immune-cell alterations may become persistent if treatment is further delayed. These findings suggest that treatment should be initiated early in patients with Gaucher disease as a means to reverse any immune irregularities and avoid the appearance of persistent effects.6
C-ANPROM/INT//7566; Date of preparation: September 2020
BURDEN OF DISEASE
Are haematological malignancies associated with Gaucher disease?
Patients with Gaucher disease may have an increased risk of developing certain types of cancer, particularly multiple myeloma and haematological malignancies.
BURDEN OF DISEASE
What neurological disorders have been linked to Gaucher disease?
The risk of developing Parkinson’s disease is increased in patients with Gaucher disease, compared with the general population.
BURDEN OF DISEASE
Have metabolic disorders been linked to Gaucher disease?
Gaucher disease is recognised as a multisystemic chronic disease where clinical symptoms can be accompanied by metabolic and hormonal disturbances.
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