Utility of multiple myeloma screening in Gaucher disease

Abstract

Gaucher disease (GD) is a lysosomal storage disease characterized by deficiency of glucocerebrosidase within lysosomes, altering degradation of glycosphingolipids, which causes accumulation of glycosylceramide. Patients with GD type 1 (GD1) have an increased incidence of gammopathy (i.e., hypergammaglobulinemia, monoclonal gammopathy of undetermined significance [MGUS]), and multiple myeloma (MM) when compared to the general population. No formal evaluation of gammopathy screening has been reported in the literature. We conducted an IRB approved retrospective analysis of clinical and laboratory data, including screening for MM, in adults with GD at Cincinnati Children’s Hospital Medical Center between 2010 and 2018. During the 8-year study period, 20 adults with GD (11 females/9 males) ages 19 to 71 (mean = 51.95 years) were screened for MM using serum protein electrophoresis (SPE) and immunofixation (IFE). Of those, 10 were treated with substrate reduction therapy (SRT) and 9 with enzyme therapy (ET). We identified no patients with MM, 2 with MGUS, and 1 with persistent polyclonal gammopathy. The 2 MGUS patients were 48 and 61 years-old, female and male respectively, with intact spleens. SPE and IFE follow-up has been stable without progression. The polyclonal gammopathy patient was a 54-year-old splenectomized male. All patients with abnormal SPE or IFE were on therapy (2 ET/ 1 SRT). Only one abnormal patient’s GBA genotype was known (p.Asn409Ser, p.Leu483Pro). Other SPE abnormalities included slight increases/decreases in albumin, protein, and beta globulin, or slight decreases in alpha 2 or gamma globulin without clinical significance. Family history of cancer was documented in 10 individuals, with no MM or blood-related malignancies reported. Our data show that as in the general population and previous GD studies, gammopathies are more common in patients greater than 50 years. These data support screening in GD1 for gammopathy greater than age 40 years.