Objectives: To define the underlying cause of unusual fast albumin bands detected on plasma protein electrophoresis of two patients.

Method: Plasma was examined by electrospray time-of-flight mass spectrometry (TOF MS) to assess the possibility of congenital or acquired structural modifications.

Results: In one patient whole protein MS indicated a drop of 486Da in the mass of 5.1% of the albumin molecules. This and the presence of an additional minor product (65,806Da) lacking a C-terminal phenylalanine (-147Da) indicated that this was albumin Rugby Park; an electrophoretically fast albumin variant caused by a splice site mutation (GT>CT) in intron 13 of the albumin gene. The second patient had an acquired alteration with a drift of albumin mobility to the anode. This severely ill patient was on intra venous antibiotics and electrospray TOF MS showed a stuttered repetition of the 66,439/66,558Da albumin isoforms at multiples of 455-459Da corresponding to the covalent attachment of 1, 2, 3 and 4 molecules of flucloxacillin. This modification of +455Da was also detected in a control on a 1g/day oral dose of flucloxacillin.

Conclusion: Both aberrations were associated with diminished albumin concentrations. The C-terminal truncation of Rugby Park (albumin, 29g/l) likely interferes with receptor binding and albumin scavenging, while the 20g/l albumin in the second patient was mostly due to renal disease. In both cases electrospray TOF MS proved a rapid (5min) sensitive (0.2μl plasma) and highly informative way of analysing whole plasma or serum.

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http://dx.doi.org/10.1016/j.clinbiochem.2015.09.013DOI Listing

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