Measuring holotranscobalamin II, an early indicator of negative vitamin B12 balance, by radioimmunoassay in patients with ischemic cerebrovascular disease

Abstract

Circulating homocysteine is a risk factor of cardiovascular and cerebrovascular events. Hyperhomocysteinemia may be an early indicator for vitamin B12 disorders because cobalamin is a cofactor in the remethylation process of homocysteine. Serum holotranscobalamin (holoTC II) becomes decreased before the development of metabolic dysfunction. In this study, we assessed circulating holoTC II to estimate the diagnosis of vitamin B12 deficiency in the first ischemic cerebrovascular attack. We also compared the efficacy of the measurement of plasma holoTC II with the other standard biochemical and hematological markers used to reach the diagnosis of cobalamin deficiency. Forty-five patients (age 71 years (range 35-90), 16 men/29 women) within the first ischemic cerebrovascular event were included in this prospective study. All the enrolled patients have been administered vitamin B12 1 mg intramuscular injection once a day for 10 days. At the baseline and on the tenth day of treatment, plasma levels of holoTC II and the proper biochemical and hematological markers in diagnosing cobalamin deficiency were measured. After admission, anemia and diminished serum vitamin B12 levels were determined to be only 20% (9/45) and 44% (20/45), respectively; 78% (35/45) of the patients had low serum holoTC II (<37 pmol/l). Serum homocysteine was higher in patients (49% of them) who had previously suffered a stroke. Thrombocytopenia, hypersegmentated neutrophils, and indirect hyperbilirubinemia were observed in 20% of the patients. Leukopenia and macrocytosis were not evident in any of them. In 18 of 27 patients (67%) that had low holoTC II levels after joining the study and who remained in the study until the end of cobalamin treatment, serum holoTC II levels returned to normal values. Cobalamin deficiency should be considered in patients with cerebrovascular diseases, even if anemia, elevated mean cell volume, depression of the serum cobalamin, or other classic hematological and/or biochemical abnormalities are lacking. Furthermore, measurement of serum holoTC II looks promising as a first-line of tests for diagnosing early vitamin B12 deficiency.

Relationship between the Levels of Holotranscobalamin and Vitamin B12

“…In the absence of a gold standard to detect vitamin B12 deficiency, the current laboratory tests to measure serum vitamin B12 levels may not be able to diagnose vitamin B12 deficiency in the early stages [1,[12][13][14][15]. The findings from several studies performed in different clinical settings have confirmed that serum vitamin B12 is a relatively poor marker with low sensitivity and specificity in predicting vitamin B12 status and that holoTC is a useful diagnostic indicator for this purpose [3,5].…”

“…The symptoms of vitamin B12 deficiency are variable, and these symptoms may be easily missed, particularly if the serum vitamin B12 levels are within the normal range [12,13]. In the absence of a gold standard to detect vitamin B12 deficiency, the current laboratory tests to measure serum vitamin B12 levels may not be able to diagnose vitamin B12 deficiency in the early stages [1,[12][13][14][15].…”

“…The findings from several studies performed in different clinical settings have confirmed that serum vitamin B12 is a relatively poor marker with low sensitivity and specificity in predicting vitamin B12 status and that holoTC is a useful diagnostic indicator for this purpose [3,5]. In addition, a few studies performed in different countries and ethnic groups have shown differences in the prevalence of vitamin B12 deficiency and have also revealed that holoTC is a more sensitive marker than total serum vitamin B12 for investigating vitamin B12 status [5,12,[16][17][18][19]. However, most of the previous studies were performed using radioimmunoassays, and very few studies have been performed with the more recent microparticle enzyme immunoassays.…”

Clinical Utility of Serum Holotranscobalamin Measurements in Patients with First-Ever Ischemic Stroke

“…Transcobalamin is essential for the transport of vitamin B12 from the intestine into most cells of the body, and patients lacking this protein eventually develop vitamin B12 deficiency [ 6 ]. When vitamin B12 is bound to transcobalamin, it is termed holoTC and represents the biologically active fraction of vitamin B12 that can be delivered to all DNA-synthesizing cells.…”

“…Vitamin B12 is essential for cellular metabolism, particularly for DNA synthesis and both fatty acid and amino acid metabolism. Importantly, vitamin B12 is a cofactor in homocysteine metabolism, and its deficiency may be an important cause of hyperhomocysteinemia [ 6 , 7 ], which is closely correlated to the risk of ischemic stroke as a result of the increased development of carotid plaques [ 2 ]. Vitamin B12 supplementation may contribute to stroke prevention [ 8 ], thus lowering homocysteine levels.…”