Consequences of diagnostic delays in type 1 Gaucher disease: the need for greater awareness among hematologists-oncologists and an opportunity for early diagnosis and intervention.

Gaucher disease (GD) is a progressive macrophage lipidosis capable of causing disabling and life-threatening complications. Anecdotal experiences suggest that GD may go undiagnosed for many years, leading to severe complications that are preventable or reversible by enzyme replacement therapy (ERT) with imiglucerase. We conducted surveys of patients and Hematology-Oncology specialists to assess the frequency of diagnostic delays. Additionally, we report a series of patients who suffered diagnostic delays and as a result developed disabilities including potentially life-threatening manifestations of GD. Of 136 patients surveyed, the average time from first appearance of GD symptoms to final diagnosis was 48.7 +/- 123.6 months. More than two-thirds were evaluated and managed by a hematologist-oncologist (Hem-Onc). A global survey of 406 Hem-Oncs found that only 20% considered GD in the differential diagnosis for all of its classic symptoms (cytopenia, hepatosplenomegaly, bone pain); the diagnosis considered most likely included leukemia, lymphoma, and multiple myeloma. To illustrate actual consequences of diagnostic delays, we describe 14 patients with GD who suffered from symptoms for up to 10 years before correct diagnosis. Diagnostic delays led to complications that are preventable or reversible with ERT (i.e., avascular necrosis, severe bleeding, chronic bone pain, life-threatening sepsis, pathologic fractures, growth failure, liver pathology). Patients homozygous for N370S mutation in this series were vulnerable to diagnostic delays. In conclusion, prolonged diagnostic delays occur in GD and may result in severe disease manifestations. Our findings suggest that physician education will increase the likelihood of prompt detection of GD and improve its management with ERT with imiglucerase when indicated.