Gaucher disease is not common in people with a group of disorders called plasma cell dyscrasias (PCDs), which include multiple myeloma. But screening for these disorders among Gaucher patients could be helpful, according to new research.
The study, “Screening for Gaucher disease among patients with plasma cell dyscrasias,” was published in the journal Leukemia & Lymphoma.
PCDs are characterized by the uncontrolled expansion of a population of white blood cells called plasma cells. These cells are responsible for producing antibodies that are the frontline of the body’s immune defense system.
Among these disorders is multiple myeloma, a type of blood cancer caused by the over-proliferation of a clone of plasma cells in the bone marrow, and secretion of abnormal antibodies that accumulate in the body.
As seen in prior studies, Gaucher disease patients are at risk for multiple myeloma and liver cancer. Evidence indicates that people with Gaucher have a 25 to 50 times greater risk of multiple myeloma and a 4 to 13 times greater risk of other blood cancers than those without this disease.
Supported by these findings, researchers with the National and Kapodistrian University of Athens tested the incidence of Gaucher disease among patients with PCDs.
Their study enrolled 285 PCD patients, most of whom (85.3%) had multiple myeloma. The remaining diagnoses were smoldering multiple myeloma (8.4%), amyloidosis (2.5%), Waldenstrom’s macroglobulinemia (2.1%), light chain deposition disease (1.1%), POEMS syndrome (0.7%).
Amounts of glucocerebrosidase — the enzyme that is impaired or lacking in Gaucher disease — were outside of normal levels in 21 patients, but all had normal levels of a disease biomarker called lyso-Gb1.
“Lyso-Gb1 is a highly sensitive and specific biomarker for Gaucher disease,” the researchers wrote. “Thus, a normal value effectively excludes the disease.”
However, genetic testing showed that one woman with multiple myeloma carried two mutations — identified as H225Q and D409H — in the GBA gene, both previously associated with Gaucher disease.
She had no family history of Gaucher disease but, given the risk of transmitting the mutations to her children, was given genetic counseling. Treatment for multiple myeloma, including an autologous stem cell transplant, carried no complications.
The team noted that common symptoms of Gaucher disease, such as enlarged spleen and liver, as well as bone lesions, may also be found in people with multiple myeloma or lymphoma, potentially leading to misdiagnosis.
Gaucher can also induce the activation of white blood cells, trigger metabolic changes, and lead to alterations in the bone microenvironment, which could increase the risk of PCDs.
Although only one patient with multiple myeloma was a carrier of Gaucher-related mutations, more studies in larger groups of patients are needed to reach definitive conclusions on the benefits of screening for Gaucher among people with PCDs, the investigators said.
“Inversely, screening of patients with Gaucher disease for monoclonal gammopathies [precursor conditions of myeloma] would be of greater interest,” they wrote. “Further insight into the pathogenesis of PCDs in patients with Gaucher disease may provide a stronger rationale for such approaches.”
