It Is Not Always Alcohol Abuse--A Transferrin Variant Impairing the CDT Test.
OBJECTIVE
Elevated Carbohydrate-deficient transferrin (CDT) levels are used as a biomarker in order to screen for chronic alcohol abuse. Transferrin (Tf) variants can impair methods to measure elevated CDT levels such as high-performance liquid chromatography (HPLC). We present a Tf variant affecting the second glycosylation site of Tf and the complications it causes in diagnosing alcoholism.


METHODS
A blood sample from a patient with suspected alcohol abuse was analyzed with HPLC, isoelectric focusing, electrospray ionization time-of-flight mass spectrometry (ESI-TOF-MS), immunoprecipitation and SDS-Page. Sanger sequencing of Tf was performed to detect Tf mutations.


RESULTS
HPLC, SDS-Page and IEF showed a distinctly increased disialo-Tf fraction while the tetrasialo-Tf fraction was decreased, ESI-TOF-MS confirmed these results. Sanger sequencing revealed the Tf mutation c.1889 A>C, deleting a Tf glycosylations site and thereby causing elevated disialo-Tf levels.


CONCLUSIONS
Transferrin mutations can severely impair the diagnostics of chronic alcohol abuse by causing false positive results. This has to be considered when CDT screening is used to detect alcoholism.
Universitätsklinikum Münster, Klinik und Poliklinik für Kinder- und Jugendmedizin-Allgemeine Pädiatrie, Albert Schweitzer Campus 1, Gebäude A 1, 48149 Münster, Germany.
Andrea
A
Zühlsdorf
Department of Medicine, Military Hospital Innsbruck, A-6020 Innsbruck, Austria.
Michael
M
Said
Institute of Medical and Chemical Laboratory Diagnostics (ZIMCL), University Hospital Innsbruck, Anichstraße 35, A-6020 Innsbruck, Austria.
Christoph
C
Seger
Universitätsklinikum Münster, Klinik und Poliklinik für Kinder- und Jugendmedizin-Allgemeine Pädiatrie, Albert Schweitzer Campus 1, Gebäude A 1, 48149 Münster, Germany.
Julien H
JH
Park
Universitätsklinikum Münster, Klinik und Poliklinik für Kinder- und Jugendmedizin-Allgemeine Pädiatrie, Albert Schweitzer Campus 1, Gebäude A 1, 48149 Münster, Germany.
Janine
J
Reunert
Universitätsklinikum Münster, Klinik und Poliklinik für Kinder- und Jugendmedizin-Allgemeine Pädiatrie, Albert Schweitzer Campus 1, Gebäude A 1, 48149 Münster, Germany.
Stephan
S
Rust
Osaka Medical Center and Research Institute for Maternal and Child Health, Osaka University, 840 Murodo-cho, Izumi, Osaka 594-1101, Japan.
Yoshinao
Y
Wada
Universitätsklinikum Münster, Klinik und Poliklinik für Kinder- und Jugendmedizin-Allgemeine Pädiatrie, Albert Schweitzer Campus 1, Gebäude A 1, 48149 Münster, Germany.
Marianne
M
Grüneberg
Universitätsklinikum Münster, Klinik und Poliklinik für Kinder- und Jugendmedizin-Allgemeine Pädiatrie, Albert Schweitzer Campus 1, Gebäude A 1, 48149 Münster, Germany.
Ingrid
I
DuChesne
Universitätsklinikum Münster, Klinik und Poliklinik für Kinder- und Jugendmedizin-Allgemeine Pädiatrie, Albert Schweitzer Campus 1, Gebäude A 1, 48149 Münster, Germany marquat@uni-muenster.de.
Thorsten
T
Marquardt
D000437:Alcoholism / Q000175:diagnosis* / Q000235:genetics*; D015415:Biomarkers / Q000032:analysis; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D014644:Genetic Variation / Q000235:genetics*; D006801:Humans; D009154:Mutation / Q000235:genetics*; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods; D014168:Transferrin / Q000031:analogs & derivatives / Q000032:analysis / Q000235:genetics*
D015415:Biomarkers; D014168:Transferrin; C056759:carbohydrate-deficient transferrin