Gamma heavy chain disease in a patient with diabetes and chronic renal insufficiency: diagnostic assessment of the heavy chain fragment

Heavy chain diseases are rare B-cell disorders that are characterized by an overproduction of abnormal and structurally incomplete monoclonal immunoglobulin (Ig) heavy chains and are devoid of light chains. We describe a case of a 62 year-old African-American woman with a long history of poorly controlled type 2 diabetes and subsequent probable diabetic nephropathy, hypertension, and recent onset of peripheral neuropathy involving all extremities. Routine laboratory testing revealed a distinct beta spike by urine protein electrophoresis (UPEP). No serum abnormality was noted on serum protein electrophoresis (SPEP). Serum and urine immunofixation demonstrated an IgG heavy chain protein devoid of any corresponding light chains. IgG subclasses identified IgG1 as the predominant IgG component but when we added all the subclasses, the sum, 683.4 mg/dL, failed to come close to our total IgG of 1,770 mg/dL. Therefore, a urine IgG subclass determination was performed in-house and we identified a subclass 3 gamma chain. In conclusion, we portray a patient with an underlying monoclonal gamma heavy chain disease (HCD) who presented with a complex medical history. The evaluation of IgG subclasses in the context of a HCD may be limited by the capability of the test to recognize the particular IgG fragment.