Carbohydrate deficient transferrin

Desialo (DST ), (English: Carbohydrate - Deficient Transferrin, CDT) is a variant of the glycoprotein transferrin, which is found in every human serum and plays an important role as an iron transport protein. Desialo also serves as a biomarker for the diagnosis of alcohol consumption. Laboratory markers for use as alcohol feed is susceptible to interference, for example at elevated gamma -GT value.

Occurrence

As a glycoprotein, the transferrin molecule carries at several points carbohydrate side chains, sialic acid residues which have. Normally in human blood transferrin isoforms come with two ( di- Sialotransferrin ) to six ( hexa- Sialotransferrin ) sialic acid residues before. Tetra Sialotransferrin ( four sialic acid residues ) usually forms the main part.

Moreover, there are genetic variants of transferrin.

Changes in alcohol intake

The structure of transferrins is changed with increasing alcohol consumption in a typical way. It is mainly to increased loss of total carbohydrate side chains. Here, the transfer of the mannose carbohydrate chain precursor, which is attached to dolichol phosphate, disrupted. Also effected by excessive and prolonged alcohol consumption, a change of the various glycosyltransferases that have a further change in the carbohydrate chains result. Due to this change in glycosylation ( carbohydrate pattern ) the CDT concentration increases sharply ( normal value man about 20 U / l, women 26 U / l, increased from 30 to > 60 U / l). Thus, the relative proportion of di-, mono-and A- Sialotransferrins (two, one or zero side chains) to. As CDT the sum of these shares is referred to by transferrins.

CDT as a laboratory parameters

CDT can be used as a laboratory tool in the diagnosis of alcoholism (or the detection of alcohol abuse). Increased CDT values ​​can be found by at least one-week intake of more than 60 g of alcohol (ethanol ) per day, equivalent to approximately 0.75 liters of wine or 1.5 liters of beer. Even after alcohol abstinence, the values ​​remain for some time (two to four weeks) increased with a half-life of 14-17 days. CDT is said to have a sensitivity of 81-93 % and a specificity of 98%. However, were even in 2001, despite decades of awareness, expressed doubts about the relevance of the method in a review and called for necessary basic research.

In the evaluation and comparison of CDT measurement results is to be noted that each method has different normal ranges, and each measured value is, therefore, to be assessed with respect to its normal range. As a relative measure of the percentage of the total is used for the CDT transferrin. With HPLC measured reference values ​​are below 1.75% (BIO- RAD test: below 2.6 %). Men, about 60 g alcohol / day for at least three weeks consume ( women over 50 g / day for two weeks) may reach a CDT content of up to 18%.

The determination of the CDT value is displayed in the following cases:

• Differential diagnosis of alcohol -induced versus non -alcoholic induced diseases (pancreatitis, liver cirrhosis, carcinoma, gastritis )
• Differential diagnosis of elevated GGT values
• Re- issuing of driving license in accordance with Regulation
• Forensic toxicological assessment of accidents and deaths related to alcohol

Analysis

For laboratory analysis, different methods are used: HPLC ( high performance liquid chromatography ), anion-exchange column chromatography with immunological transferrin determination, IEF ( isoelectric focusing), capillary electrophoresis and antibody- based detection of asialo- forms. The determination of the ratio of transferrin and CDT on the coupling of HPLC and mass spectrometry permitted the most meaningful detection of Carbohydrate Deficient transferrin (FDA standard).

HPLC and capillary electrophoresis allows the quantification of individual fractions and the detection of genetic variations. IEF is the method with the highest discriminatory power, but does not allow reliable quantification. Wherein anion-exchange column chromatography using an immunological determination of transferrin (BIO- RAD method) genetic variants can in principle not be detected. It must therefore be carried out ( eg HPLC ) confirmation of positive (pathologic ) findings by another method.