scholarly journals Measurement of Total Vitamin B12 and Holotranscobalamin, Singly and in Combination, in Screening for Metabolic Vitamin B12 Deficiency

2006 ◽  
Vol 52 (2) ◽  
pp. 278-285 ◽  
Author(s):  
Joshua W Miller ◽  
Marjorie G Garrod ◽  
Alan L Rockwood ◽  
Mark M Kushnir ◽  
Lindsay H Allen ◽  
...  
Keyword(s):  
Diagnostic Accuracy ◽  
Vitamin B12 ◽  
Methylmalonic Acid ◽  
Vitamin B12 Deficiency ◽  
Reference Intervals ◽  
Plasma Vitamin ◽  
Roc Curve Analysis ◽  
Total Vitamin ◽  
B12 Deficiency ◽  
Elderly Cohort

Abstract Background: The standard screening test for vitamin B12 deficiency, measurement of total plasma vitamin B12, has limitations of sensitivity and specificity. Plasma vitamin B12 bound to transcobalamin (holoTC) is the fraction of total vitamin B12 available for tissue uptake and therefore has been proposed as a potentially useful alternative indicator of vitamin B12 status. Methods: We compared the diagnostic accuracy of total vitamin B12, holoTC, and a combination of both measures to screen for metabolic vitamin B12 deficiency in an elderly cohort (age ≥60 years). Plasma methylmalonic acid and homocysteine were used as indicators of vitamin B12 deficiency. Results: Low total vitamin B12 (<148 pmol/L) and low holoTC (<35 pmol/L) were observed in 6.5% and 8.0%, and increased methylmalonic acid (>350 nmol/L) and homocysteine (>13 μmol/L) were observed in 12.1% and 17.0% of the study participants. In multiple regression models, holoTC explained 5%–6% more of the observed variance in methylmalonic acid and homocysteine than did total vitamin B12 (P ≤0.004). ROC curve analysis indicated that total vitamin B12 and holoTC were essentially equivalent in their ability to discriminate persons with and without vitamin B12 deficiency. Individuals with low concentrations of both total vitamin B12 and holoTC had significantly higher concentrations of methylmalonic acid and homocysteine than did individuals with total vitamin B12 and/or holoTC within the reference intervals (P <0.001). Conclusions: HoloTC and total vitamin B12 have equal diagnostic accuracy in screening for metabolic vitamin B12 deficiency. Measurement of both holoTC and total vitamin B12 provides a better screen for vitamin B12 deficiency than either assay alone.

scholarly journals Age dependency of plasma vitamin B12 status markers in Dutch children and adolescents

2021 ◽  
Author(s):  
M. Rebecca Heiner-Fokkema ◽  
Ineke J. Riphagen ◽  
Nicole S. Wiersema ◽  
Jelmer J. van Zanden ◽  
Jenny E. Kootstra-Ros ◽  
...  
Keyword(s):  
Young Children ◽  
Vitamin B12 ◽  
Reference Values ◽  
Methylmalonic Acid ◽  
Early Recognition ◽  
Vitamin B12 Deficiency ◽  
Reference Intervals ◽  
Cobalamin Deficiency ◽  
Plasma Vitamin ◽  
B12 Deficiency

Abstract Background Vitamin B12 deficiency in children may be associated with (severe) neurological manifestations, therefore recognition is important. Diagnosing vitamin B12 deficiency in children is challenging. This study aimed to investigate plasma methylmalonic acid, holotranscobalamin, and total cobalamin in children 0–18 years of age and to estimate age-dependent reference intervals. Methods Plasma vitamin B12 markers were measured in collected plasma samples of 170 children 0–18 years visiting a local primary care laboratory. All had within-reference hemoglobin and MCV values. Pediatric plasma vitamin B12 biomarkers were measured and reference values were derived thereof. Results Plasma methylmalonic acid was higher in young children, in particular between 1 and 6 months of age; total cobalamin and holotranscobalamin were highest from 0.5 to 4 years and decreased till 10 years of age. Plasma holotranscobalamin was highly correlated with plasma total cobalamin; their ratio was independent of age. Plasma methylmalonic acid was slightly more related to total cobalamin than to holotranscobalamin. A large proportion of mainly young children would be misclassified when adult references are applied. Conclusions Pediatric reference values for cobalamin markers are necessary to allow for early recognition and monitoring of children suspect of (clinical) cobalamin deficiency. Impact We analyzed three plasma vitamin B12 status markers, i.e., total cobalamin, holotranscobalamin, and methylmalonic acid, in the plasma of 170 children 0–18 years of age and were able to derive reference intervals thereof. Recognition of vitamin B12 deficiency in children is important but challenging as pediatric reference intervals for plasma vitamin B12 status markers, particularly plasma holotranscobalamin, are not well described. We think that our results may help early recognition and monitoring of children suspect of (clinical) vitamin B12 deficiency.

scholarly journals Diagnostic Performances of Urinary Methylmalonic Acid/Creatinine Ratio in Vitamin B12 Deficiency

2020 ◽  
Vol 9 (8) ◽  
pp. 2335 ◽  
Author(s):  
Sopak Supakul ◽  
Floris Chabrun ◽  
Steve Genebrier ◽  
Maximilien N’Guyen ◽  
Guillaume Valarche ◽  
...  
Keyword(s):  
Renal Impairment ◽  
Vitamin B12 ◽  
Methylmalonic Acid ◽  
Vitamin B12 Deficiency ◽  
Plasma Homocysteine ◽  
Plasma Vitamin ◽  
Creatinine Ratio ◽  
Normal Range ◽  
B12 Deficiency ◽  
High Degree

Sole measurement of plasma vitamin B12 is no longer enough to identify vitamin B12 (B12) deficiency. When plasma vitamin B12 is in the low-normal range, especially between 201 and 350 ng/L, B12 deficiency should be assessed by measurements of plasma homocysteine and/or plasma methylmalonic acid (MMA). However, these biomarkers also accumulate during renal impairment, leading to a decreased specificity for B12 deficiency. In such cases, urinary methylmalonic acid/creatinine ratio (uMMA/C) could be of interest, due to the stable urinary excretion of MMA. The objectives were to evaluate the influence of renal impairment on uMMA/C compared to plasma homocysteine and plasma methylmalonic acid, and to determine the diagnostic performances of uMMA/C in the diagnosis of B12 deficiency. We prospectively studied 127 patients with a plasma B12 between 201 and 350 ng/L. We noticed that uMMA/C was not dependent on renal function (p = 0.34), contrary to plasma homocysteine and plasma methylmalonic acid. uMMA/C showed a perspective diagnostic performance (AUC 0.71 [95% CI: 0.62–0.80]) and the threshold of 1.45 umol/mmol presented a high degree of specificity (87.9% [95% CI: 72.0–98.9]). In conclusion, uMMA/C is a promising biomarker to assess vitamin B12 status in doubtful cases, notably during renal impairment.

The relationship between the cobalt nutrition of ewes and the vitamin B12 status of ewes and their lambs

1987 ◽  
Vol 38 (6) ◽  
pp. 1071 ◽  
Author(s):  
MF Quirk ◽  
BW Norton
Keyword(s):  
Vitamin B12 ◽  
Milk Production ◽  
Acid Concentration ◽  
Methylmalonic Acid ◽  
Vitamin B12 Deficiency ◽  
Lactation Performance ◽  
Lower Productivity ◽  
Cotton South ◽  
B12 Deficiency ◽  
The Relationship

An experiment was undertaken at Mt Cotton, south-east Queensland, to investigate the relationship between the cobalt nutrition of ewes and the occurrence of vitamin B12 deficiency in ewes and their lambs. Ewes received either no supplementary cobalt (C), 0.03 mg cobalt day-1 (LC), 0.06 mg cobalt day-1 (HC) or a cobalt bullet and grinder (CB). LC and HC ewes received their supplement as a weekly drench. Supplementation commenced prior to joining, and ewes subsequently grazed pangola grass pastures containing between 0.05 and 0.11 mg kg-1 cobalt.Cobalt supplementation of ewes increased their liveweight, reproductive and lactation performance. The milk production of ewes was influenced by the level of supplementation, with C, LC, HC and CB ewes producing 31.1, 41.5, 47.7 and 50.31. of milk respectively during the first 4 weeks of lactation. The lower productivity of C ewes was associated with concentrations of vitamin B12 in serum of less than 200 pg ml-1 and with the presence of detectable concentrations of methylmalonic acid (>80 8moles l-1) and formiminoglutamic acid (>30 8moles l-1) in their urine.The growth of lambs was influenced by the cobalt nutrition of their dams; the mean liveweight gain from birth to weaning (14 weeks of age) for lambs from C, LC, HC and CB ewes was 95, 158, 194 and 231 g day-1. Vitamin B12 deficiency was evident in lambs reared by C ewes from 4 weeks of age, but lambs from LC and HC ewes did not become deficient until 8 and 12 weeks of age respectively. Lambs from CB ewes remained free of signs of deficiency prior to weaning. Urinary formiminoglutamic acid concentration was a more reliable indicator of vitamin B12 status in young lambs than urinary methylmalonic acid concentration. The concentrations of vitamin B12 in the serum of lambs were low in all groups (< 150 pg ml-1) and were generally unaffected by the cobalt nutrition of their dams.A dietary cobalt intake of about 0.15 mg day-1 appeared to be necessary for optimal milk production from ewes. However, this level of dietary cobalt was inadequate for provision of sufficient quantities of maternal vitamin B12 to meet the requirements of lambs in the later stages of lactation.

scholarly journals The Level of Serum Pepsinogen in Diagnosing and Evaluating the Severity of Subacute Combined Degeneration Due to Vitamin B12 Deficiency

2021 ◽  
Vol 12 ◽  
Author(s):  
Xiaoyan Chen ◽  
Rong Wang ◽  
Xusheng Huang ◽  
Fei Yang ◽  
Shengyuan Yu
Keyword(s):  
Vitamin B12 ◽  
Neurological Complication ◽  
Vitamin B12 Deficiency ◽  
Inverse Correlation ◽  
Cobalamin Deficiency ◽  
Serum Pepsinogen ◽  
Roc Curve Analysis ◽  
Subacute Combined Degeneration ◽  
B12 Deficiency ◽  
Autoimmune Atrophic Gastritis

Subacute combined degeneration (SCD) is a neurological complication of cobalamin deficiency, which is usually caused by chronic autoimmune atrophic gastritis. Serum pepsinogen 1 and the ratio of pepsinogen 1/pepsinogen 2 (PG1/2) can reflect the severity of gastric atrophy.Objective: This work aims to investigate whether decreased serum PG1 and PG1/2 ratio are helpful in diagnosing SCD and reflecting the severity of SCD.Methods: We retrospectively analyzed the clinical and laboratory tests of 65 cases of SCD due to vitamin B12 deficiency and compared the laboratory parameters of SCD with 65 age- and sex-matched amyotrophic lateral sclerosis (ALS) patients.Results: PG1 and PG1/2 ratio were decreased in 80 and 52.3% of SCD patients, respectively. Compared to patients with PG1/2 ratio ≥3.0, patients with PG1/2 ratio &lt;3.0 had more severe anemia, larger mean corpuscular volume (MCV), lower level of vitamin B12, higher folate and homocysteine (Hcy), more severe changes in somatosensory evoked potential (SEP), and higher rate of lesions in spinal MRI (P &lt; 0.05). PG1 and PG1/2 ratio had inverse correlation with MCV and N20 latency in SEP examination (P &lt; 0.05). PG1/2 ratio, RBC count, and Hcy were independent risk factors for SCD in logistic regression analyses. The ROC curve analysis revealed that the diagnostic accuracy of PG1 and PG1/2 ratio was 72.2 and 73.0%, respectively, while the cutoff values were 22.4 ng/ml and 2.43 for SCD, respectively.Conclusions: Decreased PG1 and PG1/2 ratio are helpful for the diagnosis and evaluation of the severity of SCD due to vitamin B12 deficiency.

scholarly journals Improved testing for vitamin B12 deficiency: correcting MMA for eGFR reduces the number of patients classified as vitamin B12 deficient

2018 ◽  
Vol 55 (6) ◽  
pp. 685-692 ◽  
Author(s):  
Saskia LM van Loon ◽  
Anna M Wilbik ◽  
Uzay Kaymak ◽  
Edwin R van den Heuvel ◽  
Volkher Scharnhorst ◽  
...  
Keyword(s):  
Data Mining ◽  
Vitamin B12 ◽  
Methylmalonic Acid ◽  
Vitamin B12 Deficiency ◽  
The Elderly ◽  
Vitamin B ◽  
Data Mining Approach ◽  
Number Of Patients ◽  
B12 Deficiency ◽  
The Relationship

Background Methylmalonic acid (MMA) can detect functional vitamin B12 deficiencies as it accumulates early when intracellular deficits arise. However, impaired clearance of MMA from blood due to decreased glomerular filtration rate (eGFR) also results in elevated plasma MMA concentrations. Alternative to clinical trials, a data mining approach was chosen to quantify and compensate for the effect of decreased eGFR on MMA concentration. Methods Comprehensive data on patient’s vitamin B12, eGFR and MMA concentrations were collected ( n = 2906). The relationship between vitamin B12, renal function (eGFR) and MMA was modelled using weighted multiple linear regression. The obtained model was used to estimate the influence of decreased eGFR on MMA. Clinical impact was examined by comparing the number of patients labelled vitamin B12 deficient with and without adjustment in MMA. Results Adjusting measured MMA concentrations for eGFR in the group of patients with low-normal vitamin B12 concentrations (90–300 pmol/L) showed that the use of unadjusted MMA concentrations overestimates vitamin B12 deficiency by 40%. Conclusions Through a data mining approach, the influence of eGFR on the relation between MMA and vitamin B12 can be quantified and used to correct the measured MMA concentration for decreased eGFR. Especially in the elderly, eGFR-based correction of MMA may prevent over-diagnosis of vitamin B12 deficiency and corresponding treatment.

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