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1 BioScientia, Institut für Laboruntersuchungen Ingelheim GmbH, Konrad-Adenauer-Strasse 17, D-55218 Ingelheim, Germany. Fax 49-6132-781-428; arndt{at}bioscientia.de
Background: Carbohydrate-deficient transferrin (CDT) is used for diagnosis of chronic alcohol abuse. Some 200–300 reports on CDT have been published in impact factor-listed journals. The aims of this review were to condense the current knowledge and to resolve remaining issues on CDT.
Approach: The literature (1976–2000) was searched using MEDLINE and Knowledge Server with "alcohol and CDT" as the search items. The data were reviewed systematically, checked for redundancy, and organized in sequence based on the steps involved in CDT analysis.
Content: The review is divided into sections based on microheterogeneity of human serum transferrin (Tf), definition of CDT, structure of human serum CDT, pathomechanisms of ethanol-induced CDT increase, preanalysis, analysis, and medical interpretation (postanalysis). Test-specific cutoff values for serum CDT and causes of false positives and negatives for chronic alcohol abuse are discussed and summarized.
Summary: Asialo- and disialo-Fe2-Tf, which lack one or two complete N-glycans, and monosialo-Fe2-Tf (structure remains unclear) are collectively referred to as CDT. Diminished mRNA concentration and glycoprotein glycosyltransferase activities involved in Tf N-glycan synthesis and increased sialidase activity most likely account for alcohol-induced increases in CDT. Knowledge about in vivo and in vitro effects on serum CDT is poor. Reliable CDT and non-CDT fractionation is needed for CDT measurement. Analysis methods with different analytical specificities and recoveries decreased the comparability of values and statistical parameters of the diagnostic efficiency of CDT. CDT is the most specific marker of chronic alcohol abuse to date. Efforts should concentrate on the pathomechanisms (in vivo), preanalysis, and standardization of CDT analysis.
The following articles in journals at HighWire Press have cited this article:
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  J. P. Bergstrom and A. Helander Clinical Characteristics of Carbohydrate-Deficient Transferrin (%Disialotransferrin) Measured by HPLC: Sensitivity, Specificity, Gender Effects, and Relationship with other Alcohol Biomarkers Alcohol Alcohol., July 1, 2008; 43(4): 436 - 441. [Abstract] [Full Text] [PDF]
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A. Helander and G. Nordin Insufficient Standardization of a Direct Carbohydrate-Deficient Transferrin Immunoassay Clin. Chem., June 1, 2008; 54(6): 1090 - 1092. [Full Text] [PDF]
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C. Perez-Cerda, D. Quelhas, A. I. Vega, J. Ecay, L. Vilarinho, and M. Ugarte Screening Using Serum Percentage of Carbohydrate-Deficient Transferrin for Congenital Disorders of Glycosylation in Children with Suspected Metabolic Disease Clin. Chem., January 1, 2008; 54(1): 93 - 100. [Abstract] [Full Text] [PDF]
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 D. Nedelkov, D. A. Phillips, K. A. Tubbs, and R. W. Nelson Investigation of Human Protein Variants and Their Frequency in the General Population Mol. Cell. Proteomics, July 1, 2007; 6(7): 1183 - 1187. [Abstract] [Full Text] [PDF]
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J. R. Delanghe, A. Helander, J. P.M. Wielders, J. M. Pekelharing, H. J. Roth, F. Schellenberg, C. Born, E. Yagmur, W. Gentzer, and H. Althaus Development and Multicenter Evaluation of the N Latex CDT Direct Immunonephelometric Assay for Serum Carbohydrate-Deficient Transferrin Clin. Chem., June 1, 2007; 53(6): 1115 - 1121. [Abstract] [Full Text] [PDF]
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J. HIETALA, H. KOIVISTO, P. ANTTILA, and O. NIEMELA COMPARISON OF THE COMBINED MARKER GGT-CDT AND THE CONVENTIONAL LABORATORY MARKERS OF ALCOHOL ABUSE IN HEAVY DRINKERS, MODERATE DRINKERS AND ABSTAINERS Alcohol Alcohol., September 1, 2006; 41(5): 528 - 533. [Abstract] [Full Text] [PDF]
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F. Bortolotti, G. De Paoli, J. P. Pascali, M. T. Trevisan, M. Floreani, and F. Tagliaro Analysis of Carbohydrate-Deficient Transferrin: Comparative Evaluation of Turbidimetric Immunoassay, Capillary Zone Electrophoresis, and HPLC Clin. Chem., December 1, 2005; 51(12): 2368 - 2371. [Full Text] [PDF]
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B. M.R. Appenzeller and R. Wennig Altered Distribution of Transferrin Isoforms According to Serum Storage Conditions Clin. Chem., November 1, 2005; 51(11): 2159 - 2162. [Full Text] [PDF]
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A. Helander, J. P.M. Wielders, R. te Stroet, and J. P. Bergstrom Comparison of HPLC and Capillary Electrophoresis for Confirmatory Testing of the Alcohol Misuse Marker Carbohydrate-Deficient Transferrin Clin. Chem., August 1, 2005; 51(8): 1528 - 1531. [Full Text] [PDF]
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J.-B. Daeppen, F. Anex, B. Favrat, A. Bissery, J. Leutwyler, R. Gammeter, P. Mangin, and M. Augsburger Carbohydrate-Deficient Transferrin Measured by Capillary Zone Electrophoresis and by Turbidimetric Immunoassay for Identification of Young Heavy Drinkers Clin. Chem., June 1, 2005; 51(6): 1046 - 1048. [Full Text] [PDF]
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C. Papadea and R. J. Schlosser Rapid Method for {beta}2-Transferrin in Cerebrospinal Fluid Leakage Using an Automated Immunofixation Electrophoresis System Clin. Chem., February 1, 2005; 51(2): 464 - 470. [Abstract] [Full Text] [PDF]
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I. Azorin, M. Portoles, P. Marin, F. Lazaro-Dieguez, L. Megias, G. Egea, and J. Renau-Piqueras PRENATAL ETHANOL EXPOSURE ALTERS THE CYTOSKELETON AND INDUCES GLYCOPROTEIN MICROHETEROGENEITY IN RAT NEWBORN HEPATOCYTES Alcohol Alcohol., May 1, 2004; 39(3): 203 - 212. [Abstract] [Full Text] [PDF]
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P. Anttila, K. Jarvi, J. Latvala, and O. Niemela METHOD-DEPENDENT CHARACTERISTICS OF CARBOHYDRATE-DEFICIENT TRANSFERRIN MEASUREMENTS IN THE FOLLOW-UP OF ALCOHOLICS Alcohol Alcohol., January 1, 2004; 39(1): 59 - 63. [Abstract] [Full Text] [PDF]
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H. A. Carchon, R. Chevigne, J.-B. Falmagne, and J. Jaeken Diagnosis of Congenital Disorders of Glycosylation by Capillary Zone Electrophoresis of Serum Transferrin Clin. Chem., January 1, 2004; 50(1): 101 - 111. [Abstract] [Full Text] [PDF]
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B. Ramdani, V. Nuyens, T. Codden, G. Perpete, J. Colicis, A. Lenaerts, J.-P. Henry, and F. J. Legros Analyte Comigrating with Trisialotransferrin during Capillary Zone Electrophoresis of Sera from Patients with Cancer Clin. Chem., November 1, 2003; 49(11): 1854 - 1864. [Abstract] [Full Text] [PDF]
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A. Helander, A. Husa, and J.-O. Jeppsson Improved HPLC Method for Carbohydrate-deficient Transferrin in Serum Clin. Chem., November 1, 2003; 49(11): 1881 - 1890. [Abstract] [Full Text] [PDF]
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P. Anttila, K. Jarvi, J. Latvala, J. E. Blake, and O. Niemela DIAGNOSTIC CHARACTERISTICS OF DIFFERENT CARBOHYDRATE-DEFICIENT TRANSFERRIN METHODS IN THE DETECTION OF PROBLEM DRINKING: EFFECTS OF LIVER DISEASE AND ALCOHOL CONSUMPTION Alcohol Alcohol., September 1, 2003; 38(5): 415 - 420. [Abstract] [Full Text] [PDF]
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T. Arndt Asialotransferrin--An Alternative to Carbohydrate-deficient Transferrin? Clin. Chem., June 1, 2003; 49(6): 1022 - 1023. [Full Text] [PDF]
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T. Arndt, D. Kuhn, H. Herbst, M. Linnemann, and N. Nikolaidis Increased Carbohydrate-deficient Transferrin of Unknown Etiology in a 15-Year-Old Male Patient with Autoimmune Hepatitis Type 1 Clin. Chem., June 1, 2003; 49(6): 1025 - 1026. [Full Text] [PDF]
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M. J. Schwarz, I. Domke, A. Helander, P. M. W. Janssens, J. van Pelt, B. Springer, M. Ackenheil, K. Bernhardt, G. Weigl, and M. Soyka MULTICENTRE EVALUATION OF A NEW ASSAY FOR DETERMINATION OF CARBOHYDRATE-DEFICIENT TRANSFERRIN Alcohol Alcohol., May 1, 2003; 38(3): 270 - 275. [Abstract] [Full Text] [PDF]
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F. J. Legros, V. Nuyens, M. Baudoux, K. Zouaoui Boudjeltia, J.-L. Ruelle, J. Colicis, F. Cantraine, and J.-P. Henry Use of Capillary Zone Electrophoresis for Differentiating Excessive from Moderate Alcohol Consumption Clin. Chem., March 1, 2003; 49(3): 440 - 449. [Abstract] [Full Text] [PDF]
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F. J. Legros, V. Nuyens, E. Minet, P. Emonts, K. Z. Boudjeltia, A. Courbe, J.-L. Ruelle, J. Colicis, F. de L'Escaille, and J.-P. Henry Carbohydrate-deficient Transferrin Isoforms Measured by Capillary Zone Electrophoresis for Detection of Alcohol Abuse Clin. Chem., December 1, 2002; 48(12): 2177 - 2186. [Abstract] [Full Text] [PDF]
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I. Ryden, P. Pahlsson, and S. Lindgren Diagnostic Accuracy of {alpha}1-Acid Glycoprotein Fucosylation for Liver Cirrhosis in Patients Undergoing Hepatic Biopsy Clin. Chem., December 1, 2002; 48(12): 2195 - 2201. [Abstract] [Full Text] [PDF]
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T. Arndt and J. Kropf Alcohol Abuse and Carbohydrate-deficient Transferrin Analysis: Are Screening and Confirmatory Analysis Required? Clin. Chem., November 1, 2002; 48(11): 2072 - 2074. [Full Text] [PDF]
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A. Helander MULTICENTRE VALIDATION STUDY OF INSTRUMENT APPLICATIONS FOR %CDT, AN IMMUNOASSAY FOR QUANTIFICATION OF CARBOHYDRATE-DEFICIENT TRANSFERRIN IN SERUM Alcohol Alcohol., May 1, 2002; 37(3): 209 - 212. [Abstract] [Full Text] [PDF]
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F. Tagliaro, F. Bortolotti, R. M. Dorizzi, M. Marigo, J. R. Delanghe, B. Wuyts, and M. L. De Buyzere Caveats in Carbohydrate-deficient Transferrin Determination Drs. Delanghe, Wuyts, and De Buyzere respond: Clin. Chem., January 1, 2002; 48(1): 208 - 209. [Full Text] [PDF]
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 H. H. Freeze Update and perspectives on congenital disorders of glycosylation Glycobiology, December 1, 2001; 11(12): 129R - 143R. [Abstract] [Full Text] [PDF]
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U. Turpeinen, T. Methuen, H. Alfthan, K. Laitinen, M. Salaspuro, and U.-H. Stenman Comparison of HPLC and Small Column (CDTect) Methods for Disialotransferrin Clin. Chem., October 1, 2001; 47(10): 1782 - 1787. [Abstract] [Full Text] [PDF]
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A. Helander, G. Eriksson, H. Stibler, and J.-O. Jeppsson Interference of Transferrin Isoform Types with Carbohydrate-deficient Transferrin Quantification in the Identification of Alcohol Abuse Clin. Chem., July 1, 2001; 47(7): 1225 - 1233. [Abstract] [Full Text] [PDF]
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