Argininosuccinate lyase deficiency (ASL) and carbohydrate-deficient transferrin (CDT): Experience with four independent CDT analysis methods — misleading results given by the %CDT TIA assay

BackgroundChronic liver disease can cause false-positive carbohydrate-deficient transferrin (CDT) results mimicking chronic alcohol abuse. We tested whether argininosuccinate lyase deficiency (ASL), a genetic disorder of the urea cycle with hepatomegaly and biochemical hepatitis, causes increased CDT results and whether this depends on the analytical method.MethodsSeven serum samples from four ASL patients without alcohol abuse were analyzed by capillary electrophoresis, HPLC, particle-enhanced immunonephelometry with monoclonal CDT antibodies, and microcolumn CDT and non-CDT fractionation followed by a turbidimetric immunoassay with transferrin antibodies (%CDT TIA).ResultsIncreased CDT results (two out of four patients or five out of seven samples) were obtained by the %CDT TIA assay, but not by the remaining three CDT tests. The corresponding serum samples showed increased fractions of trisialotransferrin by HPLC (as the IFCC reference method for CDT analysis). One sample contained an elevated trisialotransferrin but a normal CDT also in the %CDT TIA test. One patient had a normal trisialotransferrin and a normal CDT as assayed by each of the four CDT methods.ConclusionsArgininosuccinate lyase deficiency is not itself a cause for increased CDT values. Increased fractions of trisialotransferrin in ASL patients appear to interfere with CDT analysis by the %CDT TIA assay. This can give false-positive CDT results. Since this can appear not only in ASL patients, microcolumn CDT and non-CDT fractionation followed by a turbidimetric immunoassay using transferrin but not CDT antibodies by the %CDT TIA assay should no longer be used for CDT measurement without confirmatory analysis by HPLC or capillary electrophoresis.