Diagnosis of methylmalonic acidemia from dried blood spots by HPLC and intramolecular-excimer fluorescence derivatization.

Because of this specificity, a proportion of patients who are investigated for vitamin B 12 deficiency will end up being tested for the presence of IFABs, regardless of the diagnostic cascade favored by the investigating physician(s) (1, 2). In referral laboratories, this may lead to substantial test volumes of labor-intensive manual RIAs, with all the associated problems. These range from an increased risk of sample mix-ups or analytical mishaps attributable to multiple manual sample-handling steps, to difficulties in maintaining consistent performance, to the need to handle and dispose of radioactivity , and to lower analytical precision and increased turnaround time compared with automated assays. The new automated IFAB assay addresses all of these problems while maintaining comparable diagnostic accuracy. Moreover, both vitamin B 12 measurements and IFAB measurements can be performed on the same instrument, with the possibility to tag IFAB testing to individual vitamin B 12 samples, conditional on the measured cobal-amin concentration, a further improvement in workflow. We therefore believe that the availability of this new IFAB assay provides an opportunity for increased and more expeditious testing and diagnosis of pernicious anemia. The Mayo Foundation received funds from Beckman Coulter for the validation of this IF antibody assay. References 1. Snow CF. Laboratory diagnosis of vitamin B 12 and folate deficiency: a guide for the primary care physician. A randomized, double-blind, placebo-controlled study of oral vitamin B 12 supplementation in older patients with subnormal or borderline serum vitamin B 12 concentrations. Studies on a radioassay for intrinsic factor antibody: comparison of methods and false positive results due to elevated serum B 12 levels. Laboratory diagnosis of megaloblastic anaemia: current methods assessed by external quality assurance trials. Methylmalonic acidemias, a group of heterogeneous disorders , are characterized by accumulation of methylma-lonic acid (MMA) and its byproducts in biological fluids (1, 2). Methylmalonic acidemia is now included in all tandem mass spectrometry (MS/MS)-based newborn screening programs (3–5). Detection is based on the finding of increased propionylcarnitine and/or increased propionylcarnitine-to-acetylcarnitine ratio in dried blood spots (DBS) by MS/MS. These markers, however, are not specific because they are increased in propionic acidemia and, possibly, in multiple carboxylase deficiency (3). In most programs, newborns or patients with initial positive results are recalled for a second blood spot, and a urine sample is collected for organic acid analysis to differentiate among the three disorders. In the present study, we used the intramolecular-excimer fluorescence derivatization …