Consequences of Diagnostic Delays in Type 1 Gaucher Disease: A Unique Opportunity among Hematologists/Oncologists for Early Diagnosis and Intervention.
Authors: Mistry Pramod K. , Sadan Sara , Yang Ruhua , Yee John , Yang Mei 
Published: October 2019

Gaucher disease (GD) is a progressive lysosomal storage disease that can lead to life-threatening complications. Anecdotal experiences of patients and physicians suggest that symptoms and signs of the disease may go undiagnosed for many years, resulting in severe yet preventable complications. We conducted surveys of patients and Hematology/Oncology specialists to assess the frequency of diagnostic delays. Furthermore, we reviewed a series of patients in whom prolonged misdiagnosis resulted in serious complications of GD. Of 136 patients surveyed, the average time from first appearance of GD symptoms to final diagnosis was 3–4 years. Up to 86% of patients reported having visited a Hematologist/Oncologist (Hem/Onc) concerning their condition and two thirds reported current management of their symptoms by a Hem/Onc. The frequency of intial symptoms at presentation to Hem/Oncs is depicted in Table 1. In a global survey of 406 Hem/Oncs, only 20% of respondents considered GD in the differential diagnosis when presented with all six classic symptoms: anemia, thrombocytopenia, hepatomegaly, splenomegaly, bone pain, bone crisis. In contrast, the diagnoses considered more frequently for this constellation of symptoms were leukemia (65%), lymphoma (36%), and multiple myeloma (22%). When asked to list additional signs and symptoms of GD other than the six classic symptoms, 47% could not list any additional manifestations; the common signs and symptoms of easy bruising and bleeding, fatigue, and pathological fractures were identified by 9%, 5%, and 4% of respondents, respectively. Fifty-three percent of surveyed Hem/Oncs considered their specialty the best equipped to manage Gaucher patients and their self-assessed knowledge of GD on a scale of 1 (not at all knowledgeable) to 10 (extremely knowledgeable) was 4.1±2.4, with responses showing normal distribution around the mean. In a review of 14 patients with GD in whom up to 10 years elapsed from the appearance of symptoms to final diagnosis of GD, reversible or preventable complications occured including avascular necrosis, bleeding, chronic bone pain, life-threatening sepsis, pathologic fractures, growth failure and liver pathology. In this series, patients with GBA genotype N370S/N370S, which is typically associated with a mild GD phenotype, were most vulnerable to diagnostic delays. In conclusion, prolonged diagnostic delays occur frequently in GD that may result in severe complications. Physician education is needed to increase early detection of patients with GD and improve its management, and Hem/Oncs have a unique opportunity for timely diagnosis and optimal management of this treatable disorder.

Table 1. Symptoms of Patients Presenting to Hematologists/Oncologists Signs and Symptoms Percentage of Patients (n = 92) *Including thrombocytopenia, anemia, epistaxis, chronic infection, leg pain, enlarged liver and/or spleen Easy bruising or bleeding 51.1% Enlarged abdomen 46.7% Fatigue 31.5% Pain in bone and joints/bone fractures 26.1% Delayed growth 17.4% Other* 29.3%