Today we presented a case of a 44 year old M with no significant past medical history who reported a 3 month history of shortness of breath and abdominal pain and distension. Given the history and physical exam findings consistent with a volume overloaded state, the initial differential diagnosis included causes of heart failure, liver disease and renal disease (ESRD, nephrotic syndrome). Labs were significant for an infiltrative pattern of liver injury (significantly elevated alkaline phosphatase, minimally elevated transaminases and normal bilirubin) as well as an elevated globulin gap of 4.8. TTE showed reduced an ejection fraction of 35% and abdominal ultrasound demonstrated cirrhosis and ascites.
Work-up of an elevated globulin gap:
– An elevated globulin gap (difference between the total serum protein and serum albumin concentration) should always be evaluated. The first step in evaluation is to determine whether it represents a monoclonal or polyclonal gammopathy.
– Causes of polyclonal gammopathy include viral infections (acute HIV, hepatitis C), connective tissue disorders and other causes of persistent inflammation (acute phase reactants will cause an increase in the globulin gap).
– Causes of monoclonal gammopathy include MGUS, multiple myeloma, Waldenstrom’s macroglobulinemia, amyloidosis and lymphoma.
– An SPEP (shown below), immunofixation and free light chain assay should be ordered to help determine the etiology of the protein gap. Remember that SPEP is the initial screening test and the sensitivities of serum immunofixation and free light chain assay are higher for detecting the presence of paraproteins. An abnormal free light chain ratio indicates overproduction of either kappa or lambda light chain.