An enlarged spleen or low platelets counts — or both — in a person with difficult-to-diagnose complaints may be a sign of type 1 Gaucher disease (GD1), a study suggests.
Doctor should assess the activity of the beta-glucocerebrosidase enzyme — the protein defective in Gaucher disease — in dried blood spots, such as those collected for newborn screening. Combining this “simple, cheap, and easy-to-do test” with a computer algorithm that integrates three blood measures can help in identifying those with this often undiagnosed or misdiagnosed type of Gaucher disease, its researchers wrote.
The study, “Predicting the probability of Gaucher disease in subjects with splenomegaly and thrombocytopenia,” was published in the journal Scientific Reports.
Beta-glucocerebrosidase enzyme deficiency in people with Gaucher leads to the buildup of a fat molecule called glucocerebroside, which typically causes enlargement of the spleen (splenomegaly) and liver (hepatomegaly).
GD1 is the most common form of the disease, with patients often showing several blood-related abnormalities, including anemia, low platelets levels, a bleeding history, and monoclonal gammopathy of undetermined significance (MGUS), a condition characterized by the presence of an abnormal protein — called M protein — in the blood.
Due to these blood-related abnormalities, patients are often examined by hematologists, clinicians with an expertise in disorders related to the blood.
Data from an international survey, however, found that only 20% of hematologists consider the possibility of GD1 when examining a person with blood-related symptoms, bone pain, and spleen and liver enlargement. A lack of awareness of GD1 is one possible reason, another is the extensive variety of symptoms experienced, the study reported.
While the gold standard test for GD is to measure the beta-glucocerebrosidase activity in white blood cells (leukocytes) or fibroblasts, half of all patients are diagnosed after a bone marrow biopsy.
Researchers in Italy developed a computer-based algorithm that combined a dried blood spot (DBS) test to make a Gaucher diagnosis easier, especially in people with splenomegaly and/or abnormally low levels of platelets, called thrombocytopenia. The DBS test uses a dried blood sample to measure beta-glucocerebrosidase activity.
They evaluated their approach in a study of patients at 35 hematology sites in Italy. The study was open to people with splenomegaly and/or abnormally low platelet levels, plus at least one complaint related to bone pain history, anemia, spleen removal, and MGUS. Those younger than age 30 also needed evidence of polyclonal gammopathy (high levels of several different antibodies in the blood).
Overall, 455 people were included in the study’s analyses. The majority (91%) were Caucasian, with a mean age at enrollment of 46.9. About 32% were women.
Over 80% had splenomegaly (89.7%) and 47.9% had low levels of platelets, with 23.1% also having anemia. The DBS showed normal results in 379 of these people, but 76 (16.7%) had low beta-glucocerebrosidase activity.
These 76 patients plus one with family history of GD1 were then given the standard enzymatic activity test. Among the 65 with reported results, 15 were diagnosed with GD1, corresponding to a prevalence of 3.3%.
In 14 patients, a molecular analysis also revealed the presence of mutations in the GBA gene, which codes for beta-glucocerebrosidase.
These people had lower platelet counts compared to those without GD1, as well as higher ferritin levels and reduced transferrin saturation (20.8% vs 25.7%). Ferritin is the blood protein that stores iron. Measuring the levels of ferritin and transferrin saturation is a way to assess for iron deficiency.
According to three parameters that can be easily assessed in a blood sample — platelet count, ferritin, and transferrin saturation — the researchers computed a model to predict the probability of GD1 in a person showing splenomegaly and/or thrombocytopenia. Joint analysis of these three variables was deemed effective at predicting the likelihood of GD1.
“High-risk population testing is effective in identifying Gaucher disease patients who present to the hematologist with splenomegaly and/or thrombocytopenia,” the researchers wrote.
“The evaluation of the probability of having GD1 according to an equation and the use of DBS as a first-level test are potentially useful tools that can facilitate the diagnostic process,” they concluded.