Diagnostic and Disease Management Algorithms for Gaucher Disease: A Guide for Haematologists

In Gaucher disease (GD), inherited deficiency in lysosomal acid beta-glucocerebrosidase leads to the widespread accumulation of glycolipid-laden macrophages in tissues and consequent multisystemic disease. The presenting symptoms of type 1 (non neuronopathic) Gaucher disease commonly reflect the haematologic components of the disease, i.e., splenomegaly, thrombocytopenia, anaemia, and bleeding tendency. Consequently the majority of patients are referred to haematologists for diagnosis and management. However, the remarkable heterogeneity of the disease compounded by its rarity presents a diagnostic challenge. Only around 20% of haematologists consider GD in differential diagnosis even though all classic manifestations of the disease may be present. Haematologic malignancy is the most often considered diagnosis in such patients. Lack of awareness of GD and its protean manifestations renders individuals with Gaucher disease vulnerable to misdiagnosis, diagnostic delays and risk of irreversible complications that are otherwise preventable by timely therapy. Missed diagnosis may place individuals at risk of bleeding even in the presence of mild thrombocytopenia, irreversible skeletal complications leading to disability and impaired growth, and an increased risk of malignancy, especially multiple myeloma. Imiglucerase (Cerezyme) enzyme replacement therapy is effective in reversing haematological, visceral and some skeletal manifestations of the disease. In a minority of patients in whom imiglucerase is not suitable, Miglustat substrate reduction therapy (Zavesca) is an alternative. An international group of physicians met to harness their respective experience of managing the diverse phenotypes of Gaucher disease in order to raise awareness of GD and to determine under which circumstances GD should be given greater priority in differential diagnosis. As a result of their discussions, simple diagnostic algorithms have been devised, which focus on splenomegaly as the most prevalent presenting manifestation of GD in individuals of both Ashkenazi Jewish and non Ashkenazi Jewish background. Given the prevalence of GD in Ashkenazim, a possible diagnosis of GD is prioritised in the presence of splenomegaly in this population. When challenged by differential diagnosis of splenomegaly, GD can be confirmed or eliminated by a straightforward assay for beta glucocerebrosidase activity. Diagnostic algorithms are accompanied by disease management algorithms, which reflect published therapeutic goals and monitoring guidelines, to simplify decision making in the evaluation, treatment and ongoing monitoring of GD in response to therapy.