High CDT without clinical context: Beware of the variant

Carbohydrate-deficient transferrin (CDT) is a performant biomarker used for the diagnosis of chronic alcohol abuse. Here, we describe the case of a 39-year-old male of Tamil ethnicity who had extremely elevated (20%) CDT using capillary electrophoresis (but without glycoforms profile analysis), putting his driving license regranting at risk. However, the patient had no symptoms of chronic alcohol abuse, normal mean corpuscular volume and gamma-glutamyl transferase, and did not admit to any alcohol consumption. Re-analysis by N-Latex CDT immunoassay revealed a CDT at 1.7%. Further investigation by whole-exome sequencing revealed a c.1295A>G missense variant at the heterozygous state on the TFgene. This variant is characterized by an amino-acid change at a consensus sequence forN-glycosylation. Therefore, half of the patient transferrin proteins were lacking a completeN-glycan chain out of two, despite no alcohol consumption. This also explains the discrepancies between the techniques, as the NLatex antibodies did not recognize the mutated sequence. In conclusion, this case highlights the importance of comparing laboratory results between themselves and the clinical description, the absolute requirement for glycoforms profile analysis before delivering results, and the necessity to confirm intriguing results by another technique in a specialized laboratory.