Discordant Serum Folate Result Unique to the Beckman Access Assay.

Most current commercial assays for serum folate use folate-binding protein with chemiluminescence detection. Historically serum folate methods have been calibrated using pteroylglutamic acid (PGA) as this is more stable than 5Methyltetrahydrofolate (5MTHF) which is the form present in patients not receiving supplementation. Poor specificity of these binding assays together with different detection technologies and different method designs have highlighted the need for greater standardisation to calibration regimes so that individual folate species can be better identified. We describe here discrepant serum folate results in a patient which appear to be unrelated to the issues described above.

Consequent to a procurement evaluation of multiple analytical systems, serum ferritin, vitamin B12 and folate assays were performed on the Beckman Access, Abbott Architect 12000SR, Bayer Centaur and Roche E170 analysers according to manufacturer’s instructions. Method comparison studies using serum samples from 500 individuals showed good agreement between all analytical systems for all three parameters. However, one serum sample from a 44 year old Caucasian male who had presented with weight loss, diarrhoea and a microcytic, hypochromic anaemia (Hb 10.7 g/L) gave discrepant serum folate results and was further investigated. He had no evidence of renal impairment. His only medication was a multivitamin tablet supplement which he had been taking for several weeks. IgA anti-TTG antibodies were 33 U/mL (NR 0 – 10) and IgA endomysial antibodies were weakly positive. There was a polyclonal increase in serum IgA = 4.62 g/L (NR 0.8 – 2.8). Otherwise routine chemistry, thyroid profile and a paraprotein screen were unremarkable. Parietal cell and intrinsic factor antibodies were negative. Serum ferritin = 16 ng/mL (NR 20 – 215); Vitamin B12 = 164 pg/mL (NR 150–600). The patient’s sample showed no discrepant inter-system results for ferritin or Vitamin B12. Serum folate assays (NR 3.0 – 15.0 ng/mL) were as follows:

This pattern of results was confirmed on a second sample a month later. No discrepancies were found in twenty other patients with positive TTG and endomysial antibodies.

Current methods for folate assays give different results and cannot measure the various forms of folate due to lack of calibrant standardisation with different types of automated analysers. In this patient, it may be that the folate species in the Vitamin supplement are measurable by the Beckman Access but are undermeasured with the other assay techniques. This data suggests the need for a reference method capable of identifying individual folate species in all patients.