scholarly journals Elevated Homocysteine after Elevated Propionylcarnitine or Low Methionine in Newborn Screening Is Highly Predictive for Low Vitamin B12 and Holo-Transcobalamin Levels in Newborns

Diagnostics ◽  
2020 ◽  
Vol 10 (9) ◽  
pp. 626
Author(s):  
Tomaž Rozmarič ◽  
Goran Mitulović ◽  
Vassiliki Konstantopoulou ◽  
Bernadette Goeschl ◽  
Martina Huemer ◽  
...  
Keyword(s):  
Newborn Screening ◽  
Vitamin B12 ◽  
Methylmalonic Acid ◽  
Incidental Finding ◽  
Dried Blood Spots ◽  
Neurological Deficits ◽  
Spectrometric Method ◽  
Mass Spectrometric Method ◽  
Blood Spots ◽  
Total Homocysteine

Early diagnostics and treatment of vitamin B12 deficiency (B12D) in infants, mainly maternally conditioned, is crucial in preventing possible developmental delay and neurological deficits. Currently, B12D is rarely listed in regular newborn screening panels and mostly regarded as an incidental finding. The aim of this study was to evaluate a targeted newborn screening strategy for detection of suspected B12D. A decision strategy based on the primary parameters propionylcarnitine and methionine for selection of samples to be analyzed for total homocysteine by mass spectrometry was established. Therefore, 93,116 newborns were initially screened. Concentrations of vitamin B12 and holotranscobalamin in serum were obtained from clinical follow-up analyses of recalled newborns. Moreover, an extremely sensitive mass spectrometric method to quantify methylmalonic acid from the dried blood spots was developed. Overall, 0.15% of newborns were screened positive for suspected B12D, of which 64% had vitamin B12 concentrations below 148 pM. We also determined a cutoff value for methylmalonic acid in dried blood spots indicative for B12D in infants. Overall, we calculated a prevalence of 92/100,000 for suspected B12D in the Austrian newborns. In conclusion, we present a screening algorithm including second-tier measurement of total homocysteine that allows detection of low B12 serum concentrations with a high detection rate and low false-positive rate.

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.

Rapid diagnosis of phenylketonuria by quantitative analysis for phenylalanine and tyrosine in neonatal blood spots by tandem mass spectrometry

1993 ◽  
Vol 39 (1) ◽  
pp. 66-71 ◽  
Author(s):  
D H Chace ◽  
D S Millington ◽  
N Terada ◽  
S G Kahler ◽  
C R Roe ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Tandem Mass Spectrometry ◽  
Neonatal Screening ◽  
Screening Method ◽  
Dried Blood Spots ◽  
Spectrometric Method ◽  
Tandem Mass ◽  
Mass Spectrometric Method ◽  
Blood Spots ◽  
Minimal Sample

Abstract A new method for quantifying specific amino acids in small volumes of plasma and whole blood has been developed. Based on isotope-dilution tandem mass spectrometry, the method takes only a few minutes to perform and requires minimal sample preparation. The accurate assay of both phenylalanine and tyrosine in dried blood spots used for neonatal screening for phenylketonuria in North Carolina successfully differentiated infants who had been classified as normal, affected, and falsely positive by current fluorometric methods. Because the mass-spectrometric method also recognizes other aminoacidemias simultaneously and is capable of automation, it represents a useful development toward a broad-spectrum neonatal screening method.

scholarly journals Determination of Total Homocysteine, Methylmalonic Acid, and 2-Methylcitric Acid in Dried Blood Spots by Tandem Mass Spectrometry

2010 ◽  
Vol 56 (11) ◽  
pp. 1686-1695 ◽  
Author(s):  
Coleman T Turgeon ◽  
Mark J Magera ◽  
Carla D Cuthbert ◽  
Perry R Loken ◽  
Dimitar K Gavrilov ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Tandem Mass Spectrometry ◽  
False Positive ◽  
Methylmalonic Acid ◽  
False Positive Rate ◽  
Dried Blood Spots ◽  
Tandem Mass ◽  
Blood Spots ◽  
Total Homocysteine ◽  
Second Tier

BACKGROUND Newborn screening (NBS) for inborn errors of propionate, methionine, and cobalamin metabolism relies on finding abnormal concentrations of methionine and propionylcarnitine. These analytes are not specific for these conditions and lead to frequent false-positive results. More specific markers are total homocysteine (tHCY), methylmalonic acid (MMA), and methylcitric acid (MCA), but these markers are not detected by current NBS methods. To improve this situation, we developed a method for the detection of tHCY, MMA, and MCA in dried blood spots (DBSs) by liquid chromatography–tandem mass spectrometry (LC-MS/MS). METHODS The analytes were extracted from a single 4.8-mm DBS punch with acetonitrile:water:formic acid (59:41:0.42) containing dithiothreitol and isotopically labeled standards (d3-MMA, d3-MCA, d8-homocystine). The extract was dried and treated with 3 N HCl in n-butanol to form butylesters. After evaporation of the butanol, the residue was reconstituted and centrifuged and the supernatant was subjected to LC-MS/MS analysis. Algorithms were developed to apply this method as an efficient and effective second-tier assay on samples with abnormal results by primary screening. RESULTS The 99th percentiles determined from the analysis of 200 control DBSs for MMA, MCA, and HCY were 1.5, 0.5, and 9.8 μmol/L, respectively. Since 2005, prospective application of this second-tier analysis to 2.3% of all NBS samples led to the identification of 13 affected infants. CONCLUSIONS Application of this assay reduced the false-positive rate and improved the positive predictive value of NBS for conditions associated with abnormal propionylcarnitine and methionine concentrations.

Sign in / Sign up

Export Citation Format

Share Document