scholarly journals Methylmalonic acid, vitamin B12, renal function, and risk of all-cause mortality in the general population: results from the prospective Lifelines-MINUTHE study

BMC Medicine ◽  
2020 ◽  
Vol 18 (1) ◽  
Author(s):  
Ineke J. Riphagen ◽  
Isidor Minović ◽  
Dion Groothof ◽  
Adrian Post ◽  
Manfred L. Eggersdorfer ◽  
...  
Keyword(s):  
Renal Function ◽  
Vitamin B12 ◽  
Methylmalonic Acid ◽  
Vitamin B12 Deficiency ◽  
Endogenous Production ◽  
Increased Risk ◽  
B12 Deficiency ◽  
Study Population ◽  
Age And Sex

Abstract Background Methylmalonic acid (MMA) is best known for its use as a functional marker of vitamin B12 deficiency. However, MMA concentrations not only depend on adequate vitamin B12 status, but also relate to renal function and endogenous production of propionic acid. Hence, we aimed to investigate to what extent variation in MMA levels is explained by vitamin B12 and eGFR and whether MMA levels are associated with mortality if vitamin B12 and eGFR are taken into account. Methods A total of 1533 individuals (aged 60–75 years, 50% male) were included from the Lifelines Cohort and Biobank Study. Individuals were included between 2006 and 2013, and the total follow-up time was 8.5 years. Results Median [IQR] age of the study population was 65 [62–69] years, 50% was male. At baseline, median MMA concentration was 170 [138–216] nmol/L, vitamin B12 290 [224–362] pmol/L, and eGFR 84 [74–91] mL/min/1.73 m2. Log2 vitamin B12, log2 eGFR, age, and sex were significantly associated with log2 MMA in multivariable linear regression analyses (model R2 = 0.22). After a total follow-up time of 8.5 years, 72 individuals had died. Log2 MMA levels were significantly associated with mortality (hazard ratio [HR] 1.67 [95% CI 1.25–2.22], P < 0.001). Moreover, we found a significant interaction between MMA and eGFR with respect to mortality (Pinteraction < 0.001). Conclusions Only 22% of variation in MMA levels was explained by vitamin B12, eGFR, age, and sex, indicating that a large part of variation in MMA levels is attributable to other factors (e.g., catabolism, dietary components, or gut microbial production). Higher MMA levels are associated with an increased risk for mortality, independent of vitamin B12, eGFR, and sex. This association was more pronounced in individuals with impaired renal function.

Diagnostic Challenges Using a 2-Tier Strategy for Methylmalonic Acidurias: Data from 1.2 Million Dried Blood Spots

2020 ◽  
Vol 76 (4) ◽  
pp. 268-276 ◽  
Author(s):  
Katharina J. Weiss ◽  
Wulf Röschinger ◽  
Holger Blessing ◽  
Amelie S. Lotz-Havla ◽  
Katharina A. Schiergens ◽  
...  
Keyword(s):  
Vitamin B12 ◽  
Methylmalonic Acid ◽  
Vitamin B12 Deficiency ◽  
Dried Blood Spots ◽  
Maternal Vitamin ◽  
B12 Deficiency ◽  
Second Tier ◽  
Genetically Determined ◽  
Moderate Elevation

<b><i>Background:</i></b> The detection of methylmalonic acid (MMA) by second-tier analysis has been shown to reduce the number of false positives in newborn screening (NBS) for genetically determined methylmalonic acidurias (MMAuria). In addition to genetic conditions, MMA is an indicator of vitamin B12 status, thus applicable to detect maternal vitamin B12 deficiency in the newborns screened. <b><i>Methods:</i></b> Biochemical and clinical follow-up data of a 7.5-year pilot study with 1.2 million newborns screened were reviewed. <b><i>Results:</i></b> Among 1,195,850 NBS samples, 3,595 (0.3%) fulfilled criteria for second-tier analysis of MMA. In 37 (0.003%; 1/32,000) samples, elevated concentrations of MMA were detected, resulting in diagnostic workup at a metabolic center in 21 newborns. In 6 infants (1/199,000), genetic conditions were established, 1 infant with cobalamin C deficiency (CblC) showed only a moderate elevation of MMA. The remaining 15 newborns (1/79,000) displayed significantly lower concentrations of MMA and were evaluated for maternal vitamin B12 deficiency. In 9 mothers, vitamin B12 deficiency was verified, and 6 showed no indication for vitamin B12 deficiency. Treatment with vitamin B12 normalized biochemical parameters in all 15 infants. <b><i>Conclusions:</i></b> Applying a 2-tier strategy measuring MMA in NBS identified genetic conditions of MMAuria. It was possible to separate severe, early-onset phenotypes from maternal vitamin B12 deficiency. However, the detection of CblC deficiency with mildly elevated MMA interferes with impaired vitamin B12 status of unknown relevance and thus burdens possibly healthy newborns. Regarding maternal vitamin B12 deficiency, testing and supplementing mothers-to-be is preferable. This might decrease straining follow-up of newborns and improve quality and overall perception of NBS.

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.

Anemia profile in Diabetic patients with preserved renal function

2021 ◽  
Vol 12 (2) ◽  
pp. 54-58
Author(s):  
Vinay Krishnamurthy ◽  
Akhila Rao Kerekoppa
Keyword(s):  
Renal Function ◽  
General Population ◽  
Vitamin B12 ◽  
Vitamin B12 Deficiency ◽  
Deficiency Anemia ◽  
Diabetic Patients ◽  
Severe Anemia ◽  
B12 Deficiency ◽  
Anemia Of Inflammation ◽  
Prevalence Of Anemia

Background: Diabetes is one of the largest global health emergencies of the 21st century. Prevalence of anemia in diabetic patients is two to three times higher than for patients with comparable renal impairment and iron stores in the general population. Aims and Objective: This study was done to analyse the prevalence of anemia and its profile in patients with preserved renal function. Materials and Methods: One-hundred diabetic patients with anemia with normal renal functions were selected. Complete blood count, peripheral blood smear, iron studies, vitamin B12 levels were assessed. Diabetic control was monitored by HbA1c. Patients were identified to have specific type of anemia, based on iron profile and vitamin B12 levels. Severity of anemia was also assessed. Appropriate statistical tests were applied to analyse the results. Results: Mean age of subjects in the study group was 53.4±13.6 years. The mean haemoglobin level was 9.41±2.18 g/dl. Out of the 100 cases, 43 patients had iron deficiency anemia, 40 patients had anemia of inflammation, and 8 patients had vitamin B12 deficiency, 8 patients had combined iron and vitamin B12 deficiency, and 1 patient had pancytopenia. Mean HbA1c was higher in iron deficient individuals with a significant p value and mean HbA1c was lower in Vitamin B12 deficient individuals. Among the cases, 16% had mild anemia, 61% had moderate anemia, and 23% had severe anemia. Severe anemia had a significantly lower HbA1c, which was statistically significant. Conclusion: According to our study, iron deficiency anemia was the commonest, followed by anemia of inflammation in diabetic patients with preserved renal function. Diabetes being a pro-inflammatory state had a higher incidence of anemia of inflammation compared to general population. We have to identify and acknowledge the higher prevalence of Anemia of Inflammation in diabetic patients in the absence of renal dysfunction.

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.

Metabolic precursors of methylmalonic acid in vitamin B12 deficiency

1967 ◽  
Vol 18 (2) ◽  
pp. 197-204 ◽  
Author(s):  
D. Gompertz ◽  
J.Hywel Jones ◽  
J.P. Knowles
Keyword(s):  
Vitamin B12 ◽  
Methylmalonic Acid ◽  
Vitamin B12 Deficiency ◽  
B12 Deficiency ◽  
Metabolic Precursors

scholarly journals Unusual presentation of vitamin B12 deficiency in a 3 month old infant: presentation with hemolysis and thrombocytopenia

2020 ◽  
Vol 7 (8) ◽  
pp. 1816
Author(s):  
Poornima Shankar ◽  
Anil H.
Keyword(s):  
Vitamin B12 ◽  
Vitamin B12 Deficiency ◽  
Well Being ◽  
The Body ◽  
Elevated Bilirubin ◽  
B12 Deficiency ◽  
Laboratory Investigations ◽  
Vitamin B12 Supplementation ◽  
Poor Weight Gain

A 3 month old infant exclusively breast fed presented with vomiting and poor weight gain with purpuric and echymotic patches all over the body. The child also had hyperpigmentation over knuckles and icterus. Laboratory investigations revealed severe dimorphic anemia with thrombocytopenia, elevated bilirubin and LDH levels and severe vitamin B12 deficiency. Following vitamin B12 supplementation there was improvement in well-being including feed tolerance, icterus resolved and in follow up lab studies there was improvement in hemoglobin and platelet counts along with reduced bilirubin levels. Through this case report we want to emphasize the possibility of vitamin B12 deficiency presenting as hemolytic anemia and psuedothrombotic microangiopathy.

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