Are different reference intervals for methylmalonic acid and total homocysteine necessary in elderly people?

2009 ◽  
Vol 57 (3) ◽  
pp. 222-226 ◽  
Author(s):  
Etienne Joosten ◽  
Emmanuel Lesaffre ◽  
Reiner Riezler
Keyword(s):  
Elderly People ◽  
Methylmalonic Acid ◽  
Reference Intervals ◽  
Total Homocysteine

scholarly journals Age- and gender-specific reference intervals for total homocysteine and methylmalonic acid in plasma before and after vitamin supplementation

1996 ◽  
Vol 42 (4) ◽  
pp. 630-636 ◽  
Author(s):  
K Rasmussen ◽  
J Møller ◽  
M Lyngbak ◽  
A M Pedersen ◽  
L Dybkjaer
Keyword(s):  
Folic Acid ◽  
Methylmalonic Acid ◽  
Reference Intervals ◽  
Vitamin Supplementation ◽  
Specific Reference ◽  
Age And Gender ◽  
Before And After ◽  
Total Homocysteine ◽  
And Gender ◽  
Gender Specific

Abstract We present reference intervals for total homocysteine and methylmalonic acid in plasma based on samples from 126 women (ages 20-85 years, median 49 years) and 109 men (ages 20-84 years, median 50 years). The central 0.95 interval for methylmalonic acid was 0.08-0.28 micromol/L. Supplementation with cyanocobalamin caused a nonsignificant decrease in methylmalonic acid. Supplementation with folic acid caused a decrease in homocysteine concentrations, with data analysis identifying two significantly different clusters: 182 subjects with the lowest initial concentrations (7.76 +/- 1.54 micromol/L, mean +/- SD) and the smallest decrease (1.26 +/- 0.96 micromol/L), and 53 subjects with the highest initial concentrations (12.33 +/- 2.04 micromol/L) and greatest decrease (4.14 +/- 1.32 micromol/L). We argue in favor of the age- and gender-specific central 0.95 intervals obtained for the 182 subjects before being supplemented with folic acid: 4.6-8.1 micromol/L for subjects at <30 years; 4.5-7.9 micromol/L for women, ages 30-59 years; 6.3-11.2 micromol/L for men, ages 30-59 years; and 5.8-11.9 micromol/L for subjects at >60 years.

scholarly journals RIA for Serum Holo-Transcobalamin: Method Evaluation in the Clinical Laboratory and Reference Interval

2003 ◽  
Vol 49 (3) ◽  
pp. 455-462 ◽  
Author(s):  
Saila Loikas ◽  
Minna Löppönen ◽  
Pauli Suominen ◽  
Jan Møller ◽  
Kerttu Irjala ◽  
...  
Keyword(s):  
Biochemical Markers ◽  
Methylmalonic Acid ◽  
Clinical Laboratory ◽  
Reference Interval ◽  
Reference Population ◽  
Reference Intervals ◽  
Method Evaluation ◽  
Elderly Individuals ◽  
Reference Limit ◽  
Total Homocysteine

Abstract Background: Decreased serum holo-transcobalamin (holoTC) could be the earliest marker of cobalamin (Cbl) deficiency, but there has been no method suitable for routine use. We evaluated a new commercial holoTC RIA, determined reference values, and assessed holoTC concentrations in relation to other biochemical markers of Cbl deficiency. Methods: The reference population consisted of 303 individuals 22–88 years of age, without disease or medication affecting Cbl or homocysteine metabolism. In elderly individuals (≥65 years), normal Cbl status was further confirmed by total homocysteine (tHcy; <19 μmol/L) and methylmalonic acid (MMA; <0.28 μmol/L) concentrations within established reference intervals. HoloTC in Cbl deficiency was studied in a population of 107 elderly individuals with normal renal function. The Cbl deficiency was graded as potential (total Cbl ≤150 pmol/L or tHcy ≥19 μmol/L), possible (total Cbl ≤150 pmol/L and either tHcy ≥19 μmol/L or MMA ≥0.45 μmol/L), and probable (tHcy ≥19 μmol/L and MMA ≥0.45 μmol/L). Results: The intra- and between-assay imprecision (CV) for the holoTC RIA were 4–7% and 6–8%, respectively. A 95% central reference interval for serum holoTC was 37–171 pmol/L. All participants (n = 16) with probable Cbl deficiency, 86% of those with possible, and 30% of those with potential Cbl deficiency had holoTC below the reference limit (<37 pmol/L). The holoTC correlated with total Cbl (rs = 0.80; P <0.0001) and inversely with MMA (rs = −0.52; P <0.0001). HoloTC concentrations were significantly (P = 0.01) higher in women than in men. Conclusions: The new holoTC RIA is precise and simple to perform. Low holoTC is found in individuals with biochemical signs of Cbl deficiency, but the sensitivity and specificity of low holoTC in diagnosis of Cbl deficiency need to be further evaluated.

scholarly journals Plasma and Red Cell Reference Intervals of 5-Methyltetrahydrofolate of Healthy Adults in Whom Biochemical Functional Deficiencies of Folate and Vitamin B12Had Been Excluded

2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Agata Sobczyńska-Malefora ◽  
Dominic J. Harrington ◽  
Kieran Voong ◽  
Martin J. Shearer
Keyword(s):  
Methylmalonic Acid ◽  
Reference Intervals ◽  
Healthy Adults ◽  
Molecular Forms ◽  
Vitamin B ◽  
Red Cell ◽  
Relationship Of ◽  
The Relationship ◽  
Plasma Measurements ◽  
Functional Deficiency

5-Methyltetrahydrofolate (5-MTHF) is the predominant form of folate and a strong determinant of homocysteine concentrations. There is evidence that suboptimal 5-MTHF availability is a risk factor for cardiovascular disease independent of homocysteine. The analysis of folates remains challenging and is almost exclusively limited to the reporting of “total” folate rather than individual molecular forms. The purpose of this study was to establish the reference intervals of 5-MTHF in plasma and red cells of healthy adults who had been prescreened to exclude biochemical evidence of functional deficiency of folate and/or vitamin B12. Functional folate and vitamin B12status was assessed by respective plasma measurements of homocysteine and methylmalonic acid in 144 healthy volunteers, aged 19–64 years. After the exclusion of 10 individuals, values for 134 subjects were used to establish the upper reference limits for homocysteine (13 μmol/L females and 15 μmol/L males) and methylmalonic acid (430 nmol/L). Subjects with values below these cutoffs were designated as folate and vitamin B12replete and their plasma and red cell 5-MTHF reference intervals determined,N=126: 6.6–39.9 nmol/L and 223–1041 nmol/L, respectively. The application of these intervals will assist in the evaluation of folate status and facilitate studies to evaluate the relationship of 5-MTHF to disease.

scholarly journals External Quality Assessment of Methylmalonic Acid and Total Homocysteine

1999 ◽  
Vol 45 (9) ◽  
pp. 1536-1542 ◽  
Author(s):  
Jan Møller ◽  
Karsten Rasmussen ◽  
Lene Christensen
Keyword(s):  
Gas Chromatography ◽  
Quality Assessment ◽  
Methylmalonic Acid ◽  
External Quality Assessment ◽  
Mass Spectrometric ◽  
External Quality ◽  
Laboratory Component ◽  
Edta Plasma ◽  
Total Homocysteine ◽  
Minimum Quality

Abstract Background: The use of analyses for methylmalonic acid (MMA) and total homocysteine (HCY) in plasma has become widespread. Realizing the need for external quality assessment for these measurements, we started a program in 1997. The results for 1998 are reviewed in this report. Methods: Fourteen laboratories participated with 15 sets of results for MMA, and 28 laboratories participated with 34 sets of results for HCY. Results for four identical samples, made up from the same unmodified serum (MMA) or EDTA-plasma (HCY) pool, sent out under different identifications, were used for assessing the imprecision. Samples made up from the same pools supplemented with MMA or l-HCY to three concentrations were used for assessing the recovery. By using literature data for the biological variation, quality goals for both analytes were calculated. Results: The overall within-laboratory CV was 12% for MMA and 7.5% for HCY. Gas chromatography–mass spectrometric HCY results had lower imprecision than the HPLC or immunoassay results. For MMA, no significant between-laboratory component of variance was found. Only results for HCY obtained with HPLC methods showed significant between-laboratory variance. Conclusions: Eight of the 15 participants achieved the minimum imprecision goal for MMA vs 9 of the 34 participants for HCY. The minimum quality goals for bias as approximated by the recovery were achieved by 13 participants for MMA and 26 for HCY.

scholarly journals Comparative Bioavailability of Synthetic B12 and Dietary Vitamin B12 Present in Cow and Buffalo Milk: A Prospective Study in Lactovegetarian Indians

Nutrients ◽  
2019 ◽  
Vol 11 (2) ◽  
pp. 304 ◽  
Author(s):  
Namita Mahalle ◽  
Vijayshri Bhide ◽  
Eva Greibe ◽  
Christian Heegaard ◽  
Ebba Nexo ◽  
...  
Keyword(s):  
Prospective Study ◽  
Vitamin B12 ◽  
Methylmalonic Acid ◽  
Buffalo Milk ◽  
Dietary Vitamin ◽  
Comparative Bioavailability ◽  
Total Homocysteine ◽  
A Prospective Study ◽  
Oral Doses ◽  
Over Time

We assessed improvements in the vitamin B12 status of Indian lactovegetarians receiving four weeks supplementation with natural B12 in milk versus cyano-B12 in capsules. Three groups (n = 22, 23, 22) received daily oral doses of cyano-B12 (2 × 0.76 µg) or milk (2 × 200 mL) from a cow or buffalo (amounting to B12 ≈ 2 × 0.76 µg). Their blood was examined at baseline and each following week. The baselines (median (min/max)) indicated a low B12 status: plasma B12 (116(51/314)) pmol/L, holotranscobalamin (holoTC) (30(7/119)) pmol/L, total homocysteine (Hcy) (24(10/118)) µmol/L, methylmalonic acid (MMA) (0.58(0.15/2.2)) µmol/L and combined B12 index (cB12) (−1.32 − (−3.12/+0.29)). Shifts from the baselines (B12, holoTC, cB12) and ratios to the baselines (Hcy, MMA) were analyzed over time. The cyano-B12 treatment gave more total B12 in plasma at week one (+29 pmol/L, p = 0.004) but showed no further increase. Other biomarkers changed more comparably between the three groups (p ≥ 0.05): holoTC showed a transient spike that leveled off, Hcy finally decreased to 0.8 × baseline, while MMA showed marginal changes. The combined indexes improved comparably (p = 0.6) in all groups (+0.2(−0.3/+0.9), p ≤ 0.002). In conclusion, the tested formulations similarly improved B12 status, but did not normalize it.

Impairment of homocysteine metabolism in patients with retinal vascular occlusion and non-arteritic ischemic optic neuropathy

2005 ◽  
Vol 43 (10) ◽  
Author(s):  
Olaf Stanger ◽  
Martin Weger ◽  
Rima Obeid ◽  
Werner Temmel ◽  
Andreas Meinitzer ◽  
...  
Keyword(s):  
Optic Neuropathy ◽  
Methylmalonic Acid ◽  
Vascular Occlusion ◽  
Vitamin B ◽  
Ischemic Optic Neuropathy ◽  
Plasma Thcy ◽  
Retinal Vascular Occlusion ◽  
Total Homocysteine ◽  
Atherothrombotic Disease ◽  
Mild Hyperhomocysteinemia

AbstractMild hyperhomocysteinemia is established as an independent risk factor for atherothrombotic disease, including ocular pathologies such as retinal vascular occlusion and non-arteritic ischemic optic neuropathy (NAION). Low intake or low status of B-vitamins explains elevated total homocysteine (tHcy) concentrations only in part. The underlying cause for disturbed homocysteine metabolism requires further insight. We investigated whether the combined determinations of plasma tHcy, methylmalonic acid (MMA) and cystathionine provide more information on the causes of impaired homocysteine metabolism as compared with vitamin B

Determination of methylmalonic acid, 2-methylcitric acid, and total homocysteine in dried blood spots by liquid chromatography–tandem mass spectrometry: A reliable follow-up method for propionylcarnitine-related disorders in newborn screening

2020 ◽  
pp. 096914132093772
Author(s):  
Zhenzhen Hu ◽  
Jianbin Yang ◽  
Yiming Lin ◽  
Junjuan Wang ◽  
Lingwei Hu ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Tandem Mass Spectrometry ◽  
Newborn Screening ◽  
Methylmalonic Acid ◽  
Dried Blood Spots ◽  
Tandem Mass ◽  
Chromatography Tandem Mass Spectrometry ◽  
Liquid Chromatography Tandem Mass ◽  
Total Homocysteine

Objectives Determination of methylmalonic acid, 2-methylcitric acid, and total homocysteine in dried blood spots by liquid chromatography–tandem mass spectrometry has usually been used as a second-tier test to improve performance of newborn screening for propionylcarnitine-related disorders. However, factors that potentially affect its detection results have not been investigated, and we aimed to evaluate these influencing factors and explore their potential utility in newborn screening and initial follow-up for propionylcarnitine-related disorders. Methods This study comprised a prospective group (1998 healthy infants, to establish cutoff values and investigate the influencing factors) and a retrospective group (804 suspected positive cases screened from 381, 399 newborns for propionylcarnitine-related disorders by tandem mass spectrometry, to evaluate the performance of newborn screening and initial follow-up). Results Cutoff values for methylmalonic acid, 2-methylcitric acid, and total homocysteine were 2.12, 0.70, and 10.05 µmol/l, respectively. Concentration of methylmalonic acid, 2-methylcitric acid, and total homocysteine in dried blood spots is not impacted by sex, age, birth weight, gestational age, or dried blood spot storage time. A total of 75 of 804 cases were screened positive by combined tandem mass spectrometry and liquid chromatography–tandem mass spectrometry, thus eliminating 90% of the false positives without compromising sensitivity. Eighteen propionylcarnitine-related disorders were successfully identified, including one CblX case missed in the initial follow-up by tandem mass spectrometry. Conclusions Methylmalonic acid, 2-methylcitric acid, and total homocysteine detected in dried blood spots by liquid chromatography–tandem mass spectrometry is a reliable, specific, and sensitive approach for identifying propionylcarnitine-related disorders. We recommend this assay should be performed rather than tandem mass spectrometry in follow-up for propionylcarnitine-related disorders besides second-tier tests in newborn screening.

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