Carbohydrate-deficient

Alcohol consumption is very difficult to assess. There is widespread belief that individuals underreport their intake and there are no reliable laboratory tests available for definitive diagnosis of alcohol abuse. A combination of abnormalities in the plasma activity of gamma-glutamyl transferase (GGT or yGT), AST and reduction in erythrocyte mean cell volume (MCV) maybe useful and all are routine lab. tests. A potential marker of interest is carbohydrate-deficient transferrin (CDT) which is an abnormal isoform of serum transferrin arising due to defects in the attachment of carbohydrate chains to the protein core. Unfortunately, CDT is a somewhat specialized test, not performed by most laboratories. Other markers which have attracted some research interest are ethyl sulphate and ethyl glucuronide. Excretion in the urine of these metabolites occurs for up to 50 hours after binge drinking so they offer a useful index of recent heavy alcohol intake. 

Hackler R, Arndt T, Peters V, Assmann B, Hoffmann GF, Steinmetz A (1998) Automated isoelectric focusing of serum isotransferrins for laboratory diagnosis of carbohydrate deficient glycoprotein syndrome using the PhastSystem . Scand J Clin Lab Invest 58 66-67... 

Iourin O, Mattu TS, Mian N, Keir G, Winchester B, Dwek RA, Rudd PM (1996) The identification of abnormal glycoforms of serum transferrin in carbohydrate deficient glycoprotein syndrome type I by capillary zone electrophoresis. Glycoconj J 13 1031-1042... 

Jaeken J, Schachter H, Carchon, H, De Cock P, Coddeville B, Spik G (1994) Carbohydrate deficient glycoprotein syndrome type II a deficiency in Golgi localised N-acetyl-glucosami-nyltransferase II. Arch Dis Child 71 123-127... 

Jaeken J, Stibler H, Hagberg (1991) The carbohydrate-deficient glycoprotein syndrome. A new inherited multisystemic disease with severe nervous system involvement. Acta Paedi-atr Scand Suppl 375 1-71... 

Liibke T, Marquardt T, von Figura K, Korner C (1999) A new type of carbohydrate-deficient glycoprotein syndrome due to a decreased import of GDP-fucose into the Golgi. J Biol Chem 274 25986-25989... 

Niehues R, Hasilik M, Alton G, Korner C, Schiebe-Sukumar M, Koch HG, Zimmer KP, Wu R, Harms E, Reiter K, von Figura K, Freeze HH, Harms HK, Marquardt T (1998) Carbohydrate-deficient glycoprotein syndrome type lb. Phosphomannose isomerase deficiency and mannose therapy. J Clin Invest 101 1414-1420... 

Schaftingen E van, Jaeken J (1995) Phosphomannomutase deficiency is a cause of carbohydrate-deficient glycoprotein syndrome type I. FEBS Lett 377 318-320... 

Stibler H, Skovby F (1994) Failure to diagnose carbohydrate-deficient glycoprotein syndrome prenatally. Pediatr Neurol 11 71... 

Schachter, H. and Jaeken, J. (1999) Carbohydrate-deficient glycoprotein syndrome type II. Biochim. Biophys. Acta 1455(2-3), 179-192. 

De Feo, T.M., Fargion, S., Duca, L., Mattioli, M., Cappellini, M.D., Sampietro, M., Cesana, B.M., Fiorelli, G. Carbohydrate-deficient transferrin, a sensitive marker of chronic alcohol abuse, is highly influenced by body iron. Hepatology 1999 29 658-663... 

Gjerde, H., Johnsen, J., Bjorneboe, A., Bjorneboe, G.-E.A.A., Morland, J. A comparison of serum carbohydrate-deficient transferrin with other biological markers of excessive drinking. Scand. J. Lab. Invest. 1988 48 1-6... 

Nalpas, B., Hispard, E., Thepot, V., Pot, St., Dally, S., Berthelot, R A comparative study between carbohydrate-deficient transferrin and gamma-glutamyltransferase for the diagnosis of excessive drinking in a liver unit. J. Hepatol. 1997 27 1003-1008... 

Stibler, H. Carbohydrate-deficient transferrin in serum a new marker of potentially harmful alcohol consumption reviewed. Clin. Chem. 1991 37 2029-2037... 

Hepatic porphyrias show the following characteristics (1.) intermittent course, (2.) increased ALA synthase activity, and (3.) acute attacks induced or manifesting during the latency period due to numerous causes such as alcohol (281), hunger, carbohydrate deficiency, hormones, stress, intoxication, metabolic products and medicaments, (s. tab. 31.13) The diagnosis is based upon the clinical symptomatology and the excretion pattern of the porphyrins or their precursors in the urine and faeces as well as their concentrations in the erythrocytes and plasma, (s. tab. 31.14)... 

CDT is also assayed extensively, especially in Europe, for detection of alcohol abuse. Other proteins, such as tti-acid glycoprotein, are carbohydrate deficient in this case as well. The gold standard for assessment is HPLC, although both capillary electrophoresis and immunoassays are more commonly used in clinical settings. Immunoassays in particular are poorly standardized, both qualitatively and quantitatively positive tests should be confirmed by an alternative method." Genetic variants of Tf may also complicate interpretation of results. 

A. Arndt T. Carbohydrate-deficient transferrin as a marker of chronic alcohol abuse A critical review of preanalysis, analysis, and interpretation. Clin Chem 2001 47 13-27. 

A. Fleming MF, Anton RF, Spies CD. A review of genetic, biological, pharmacological, and clinical factors that affect carbohydrate-deficient transferrin levels. Alcohol Clin Exp Res 2004 28 1347-55,... 

A. Golka K, Wiese A. Carbohydrate-deficient transferrin (CDT)-a biomarker for long-term alcohol consumption. J Toxicol Environ Health B Crit Rev 2004 7 319-37. 

A. Javors MA, Johnson BA. Current status of carbohydrate deficient transferrin, total serum sialic acid, sialic acid index of apofipoprotein and serum beta-hexosaminidase as markers for alcohol consumption. Addiction 2003 98 Suppl 2 45-50. 

B. Koch H, Meerkerk GJ, Zaat JO, Ham ME, Scholten RJ, Assendelft WJ. Accuracy of carbohydrate-deficient transferrin in the detection of excessive alcohol consumption A systematic review. Alcohol Alcohol 2004 39 75-85. 

B. Niemela O, Sorvajarvi K, Blake JE, Israel Y. Carbohydrate-deficient transferrin AS. A marker of alcohol abuse. Relationship to alcohol consumption, severity of liver disease and fibrinogenesis. Alcohol Clin Esp Res 1995 19 1205-8. 

B. SiUanaukee P, Olsson U. Improved Diagnostic Classification of Alcohol Abusers by Combining Carbohydrate-deficient Transferrin and-Glutamyltransferase. Clin Chem 2001 47 681-5. 

A. Wuyts B, Delanghe IR. The analysis of carbohydrate-deficient transferrin, marker of chronic alcoholism, using capillary electrophoresis. Clin Chem Lab Med 2003 41 739-46. 

A. Yersin B, Nicolet JF, Dercrey H, Burnier M, van MeUe G, Pecoud A. Screening for excessive alcohol drinking Comparative value of carbohydrate-deficient transferrin, gamma-glutamyltransferase and mean corpuscular volume. Arch Intern Med 1995 155 1907-11. 

Several sugar-nucleotide pool defects have been identified Type I carbohydrate-deficient glycoprotein syndrome (CDGs type I), a defect in phosphomannomu-tase, one of the enzymes responsible for converting glucose to GDP-mannose, results in an absence of... 

Qualitative modifications in the glycosylation of this protein occur after prolonged heavy alcohol consumption and also in patients with rare congenital disorders of glycosylation (CDG). Therefore, measurement of transferrin microheterogeneity has been used both as a biomarker for detection and follow-up of alcohol abuse [known as carbohydrate-deficient transferrin (CDT)]" and for diagnosis of CDG. This chapter will review the microheterogeneity of human transferrin and the methods used for the measurement of transferrin... 

Figure 6.1 Structural illustration of the major normal glycoforms of human serum transferrin and those being influenced by chronic alcohol abuse (carbohydrate-deficient transferrin CDT) and in congenital disorders of glycosylation (CDG)...

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