Diagnosis of congenital dysproteinemias.

Serum protein deficiencies can be studied by qualitative, quantitative, and functional assays. Deficiencies of albumin, a ! anti trypsin (homozygous type ZZ), and IgG (especially subclass 1) can be detected easily by protein electrophoresis, whereas deficiencies of other proteins must be detected by specific immunochemical or functional assays. The diagnosis of congenital dysprotein­ emias involves qualitative, quantitative and functional tests. The qualitative test used in almost all clinical laboratories is serum electrophoresis which provides in­ formation on specific deficiencies of three proteins: albumin, anti-trypsin, and IgG. The electrophoretic separation usually is performed on either cellulose acetate membranes or agarose gels and requires only small volumes of serum, usually less than 1 microliter. Qualitative results from electrophoresis can be confirmed by quan­ titative tests which are usually immu­ nochemical assays requiring specific anti­ sera and standard preparations of the serum protein in question. Many different techniques exist for immunochemical quantitation of proteins,—the most popu­ lar being radial immunodiffusion and nephelometry. An excellent technique for the large clinical immunology laboratory is rate nephelometry and automated in­ strumentation is available commercially.* At the present time, few serum proteins need to be evaluated functionally since immunochemical activity is, in most cases, consistent with functional activity. However, this situation possibly would change in the future. The degree of struc­ tural variation in the serum proteins is clearly extensive. It is to be expected that as the quality of the antisera improves, more variant proteins will be found which are functionally deficient, even though they are antigenically intact.