The gamma gap, alternatively known as the paraprotein gap, is the difference between total serum protein concentration and the serum albumin concentration. (Total protein concentration minus albumin concentration = "gamma gap".)
The gamma gap will be increased by any process that leads to the increase in non-albumin serum proteins. An elevated gamma gap should lead to evaluation for the presence of conditions such as blood cell dyscrasias or viral infections, e.g., multiple myeloma, monoclonal gammopathy of unknown significance, or acute HIV infection.
The gamma gap is typically considered to be elevated if it is above 4 g/dL. (NB: at Hopkins, some firms want you to work up gamma gaps as modest as 3.5 g/dL). On some firms, an unexplained, elevated gamma gap virtually always triggers an SPEP, UPEP, and a serum free light chain assay.
As a matter of principle, the protein-albumin concentration difference isn't known to be a "gamma gap" until it is demonstrated that the excess protein concentration comes from gamma globulins. In practice, this is the nomenclature.
Thanks to Matt Czarny, MD
, for providing a correction regarding pure albumin-losing conditions (which lead to concomitant decrease in total protein and thus don't create a gamma gap).