During the last 16 years an increasing number of studies have indicated a new diagnostic marker of
alcohol abuse, unrelated to any of the conventional markers of
alcoholism. This marker, now called
carbohydrate-deficient transferrin, consists mainly of one or two
isoforms of
transferrin that are deficient in their terminal
trisaccharides. Such
isoforms have so far been detected by methods based on charge, i.e., isoelectric focusing, chromatofocusing, and
anion-exchange chromatography of various designs combined with immunological detection techniques. This
transferrin abnormality measures an accumulated effect of alcohol consumption, appearing after regular intake of 50-80 g of
ethanol/day for at least one week and normalizing slowly during abstinence (half-life = about 15 days). To summarize all studies to date, approximately 2500 individuals have been examined, with a total clinical sensitivity of 82% and a specificity of 97%. False-positive results have only occasionally been reported: in a few patients with severe
liver disease, usually
primary biliary cirrhosis and
chronic active hepatitis; in patients with genetic D variants of
transferrin; and in patients with (and some carriers of) a recently identified inborn error of
glycoprotein metabolism. The mechanism behind the
transferrin abnormality is unknown but an
acetaldehyde-mediated inhibition of glycosyl transfer has been suggested.
Carbohydrate-deficient transferrin may thus offer a new possibility of diagnosing
alcohol-related disorders. Its measurement is little affected by other conditions and, contrary to conventional markers of
alcohol abuse, is apparently largely independent of concomitant
liver disease.