In an article titled “Finding and Treating Gaucher Disease Type 1 – The Role of the Haematologist” that was recently published in the European Oncology & Haematology Review, the function of hematologists in finding and treating Gaucher disease type 1 was assessed and discussed.
Gaucher disease type 1 is a rare autosomal recessive disorder characterized by mutations in the GBA gene. It is the most common lysosomal storage disease, and among Ashkenazi Jews, it is the most common genetic disorder.
In the study conducted by Maria-Domenica Cappellini and colleagues from Italy and Spain, the potential to reduce the risk of long-term complications and reverse many of the initial signs/symptoms correlated with an early diagnosis and prompt management of Gaucher disease. Since unexplained splenomegaly and/or thrombocytopenia (which present in childhood) are experienced by a majority of Gaucher disease patients, hematologists and pediatricians receive the majority of initial referrals. Due to a lack of awareness surrounding rare hematological disorders, phenotypic heterogeneity, and/or mild or non-specific symptoms, physicians rarely consider Gaucher disease in their differential diagnoses. Expensive, time-consuming, and outsourced testing have been attributed to delayed diagnoses as well.
In 2 separate case studies that evaluated a proper diagnosis and misdiagnosis, the study highlighted the commonality of misdiagnosis with Gaucher disease Type 1 and the positive effects of proper diagnoses due to resulting, correct treatment. Case 1 evaluated the misdiagnosis (from childhood) of spherocytosis in a 37-year-old Caucasian woman, which resulted in an inappropriate liver biopsy and delayed appropriate management and treatment. Only after 1 year of enzyme replacement therapy (ERT) did the patient’s laboratory parameters improve.
Case 2 evaluated a proper diagnosis of a 15-monhth-old child. Due to a growth retardation, anemia, thrombocytopenia and hepatosplenomegaly suggested a lysosomal storage disease (LSD) combination, a lysosomal storage disease (LSD) was suggested. A dried blood spot (DBS) test, which revealed reduced β-glycosidase activity and molecular analysis unveiled a homozygous mutation in the GBA gene. Post Gaucher disease type 1 was diagnosis, ERT was administered. In comparison to the case 1 patient, 3 months post ERT treatment, anemia and thrombocytopenia resolved in the case 2 study patient. Additionally, up to 1-year post-treatment, hepatosplenomegaly and growth parameters improved with no side effects.
As it was proven with case study 2, an early and proper diagnosis of Gaucher disease type 1 can prevent or reverse many of the clinical features post administration of ERT therapy. However, merely 20% of physicians include Gaucher disease in their differential diagnosis of patients with classic Gaucher disease symptoms since most suspect leukaemia, lymphoma, or multiple myeloma (according to a survey of 406 haematologist–oncologists from 7 countries). As a result, the average time from symptom development to diagnosis is 4.1 ± 10.3 years.
Diagnostic clues mentioned in the study included thrombocytopenia, splenomegaly, hepatomegaly, fatigue (sometimes related to anaemia), leucopenia, bone pain/disease, growth retardation and/or delayed puberty. However, since these diagnostic clues overlap with a myriad of other diseases, they can be misleading.
Diagnostic tests to determine Gaucher disease type 1 can be performed though. The primary diagnostic test to diagnose Gaucher disease type 1 is measuring β-glucosidase activity in peripheral blood leucocytes (normal range: 2.1–5.3 μmol/l/h). However, due to the test’s expense and unavailability due to a lack of providing centers, the tandem mass spectroscopy (MS/MS) DBS assay and the fluorescence DBS assay can serve as alternatives. Molecular screenings for common GBA1 mutations, bone marrow biopsies, and biochemical markers are other diagnostic tests that can be utilized to determine Gaucher disease type 1.
The study noted that the use of simple diagnostic algorithms and newly-available DBS assays were suggested, in studies conducted in adults across Italy, to facilitate the diagnosis of Gaucher disease and avoid unnecessary biopsies, even among physicians without disease-specific expertise. In addition, evidence suggests that this may cause a reduction in the diagnostic delay and consequently encourage prompt management and subsequent improvements in both quality of life and clinical outcomes. However, in order to increase awareness regarding the benefits of prompt Gaucher disease diagnosis and management among non-Gaucher disease experts, more efforts are needed.
For more news from the rare disease community, subscribe to Rare Disease Report’s e-newsletter.