scholarly journals Differences of Phenylalanine Concentrations in Dried Blood Spots and in Plasma: Erythrocytes as a Neglected Component for This Observation

Metabolites ◽  
2021 ◽  
Vol 11 (10) ◽  
pp. 680
Author(s):  
Dorothea Haas ◽  
Jana Hauke ◽  
Kathrin V. Schwarz ◽  
Lucia Consalvi ◽  
Friedrich K. Trefz ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Venous Blood ◽  
Plasma Concentrations ◽  
Dried Blood Spots ◽  
Ion Exchange Chromatography ◽  
Exchange Chromatography ◽  
Tandem Mass ◽  
Blood Samples ◽  
Blood Spots ◽  
Edta Plasma

Monitoring phenylalanine (Phe) concentrations is critical for the management of phenylketonuria (PKU). This can be done in dried blood spots (DBS) or in EDTA plasma derived from capillary or venous blood. Different techniques are used to measure Phe, the most common being flow-injection analysis tandem mass spectrometry (FIA-MS-MS) and ion exchange chromatography (IEC). Significant differences have been reported between Phe concentrations in various sample types measured by different techniques, the cause of which is not yet understood. We measured Phe concentrations in 240 venous blood samples from 199 patients with hyperphenylalaninemia in dried blood spots, EDTA plasma and erythrocytes by FIA-MS-MS and IEC. Phe concentrations were significantly lower in erythrocytes than in plasma leading to about 19% lower Phe DBS concentrations compared with plasma independent from the method used for quantification. As most therapy recommendations for PKU patients are based on plasma concentrations reliable conversion of DBS into plasma concentrations is necessary. Variances of Phe concentrations in plasma and DBS are not linear but increases with higher concentrations indicating heteroscedasticity. We therefore suggest the slope of the 75th percentile from quantile regression as a correction factor.

scholarly journals Newborn Screening for Long-Chain 3-Hydroxyacyl-CoA Dehydrogenase and Mitochondrial Trifunctional Protein Deficiencies Using Acylcarnitines Measurement in Dried Blood Spots—A Systematic Review of Test Accuracy

2021 ◽  
Vol 9 ◽  
Author(s):  
Chris Stinton ◽  
Hannah Fraser ◽  
Julia Geppert ◽  
Rebecca Johnson ◽  
Martin Connock ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Tandem Mass Spectrometry ◽  
Dried Blood Spots ◽  
Test Accuracy ◽  
Tandem Mass ◽  
Blood Spots ◽  
Hydroxyacyl Coa Dehydrogenase ◽  
Sensitivity Specificity ◽  
Long Chain

Background: Long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) and mitochondrial trifunctional protein (MTP) deficiencies are rare autosomal recessive fatty acid β-oxidation disorders. Their clinical presentations are variable, and premature death is common. They are included in newborn blood spot screening programs in many countries around the world. The current process of screening, through the measurement of acylcarnitines (a metabolic by-product) in dried blood spots with tandem mass spectrometry, is subject to uncertainty regarding test accuracy.Methods: We conducted a systematic review of literature published up to 19th June 2018. We included studies that investigated newborn screening for LCHAD or MTP deficiencies by tandem mass spectrometry of acylcarnitines in dried blood spots. The reference standards were urine organic acids, blood acylcarnitine profiles, enzyme analysis in cultured fibroblasts or lymphocytes, mutation analysis, or at least 10-year follow-up. The outcomes of interest were sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). Assessment of titles, abstracts, and full-text papers and quality appraisal were carried out independently by two reviewers. One reviewer extracted study data. This was checked by a second reviewer.Results: Ten studies provided data on test accuracy. LCHAD or MTP deficiencies were identified in 23 babies. No cases of LCHAD/MTP deficiencies were identified in four studies. PPV ranged from 0% (zero true positives and 28 false positives from 276,565 babies screened) to 100% (13 true positives and zero false positives from 2,037,824 babies screened). Sensitivity, specificity, and NPV could not be calculated as there was no systematic follow-up of babies who screened negative.Conclusions: Test accuracy estimates of screening for LCHAD and MTP deficiencies with tandem mass spectrometry measurement of acylcarnitines in dried blood were variable in terms of PPVs. Screening methods (including markers and thresholds) varied between studies, and sensitivity, specificity, and NPVs are unknown.

Incorporating the measurement of EDTA in dried blood spots (DBS) by tandem mass spectrometry in routine newborn screening

2014 ◽  
Vol 47 (15) ◽  
pp. 144
Author(s):  
Lawrence J. Fisher ◽  
Osama Y. Al-Dirbashi ◽  
Svetlana Ogrel ◽  
Nathan McIntosh ◽  
Michael T. Geraghty ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Tandem Mass Spectrometry ◽  
Newborn Screening ◽  
Dried Blood Spots ◽  
Tandem Mass ◽  
Blood Spots

Development of a method for multiple vitamin D metabolite measurements by liquid chromatography coupled with tandem mass spectrometry in dried blood spots

The Analyst ◽  
2019 ◽  
Vol 144 (1) ◽  
pp. 299-309 ◽  
Author(s):  
R. Rola ◽  
K. Kowalski ◽  
T. Bieńkowski ◽  
A. Kołodyńska-Goworek ◽  
S. Studzińska
Keyword(s):  
Mass Spectrometry ◽  
Vitamin D ◽  
Liquid Chromatography ◽  
Tandem Mass Spectrometry ◽  
Dried Blood Spots ◽  
Tandem Mass ◽  
Vitamin D Metabolites ◽  
Blood Spots ◽  
First Time

Profiling of vitamin D metabolites in dried blood spots, including 24,25(OH)2D3, has been performed for the first time.

Rapid diagnosis of maple syrup urine disease in blood spots from newborns by tandem mass spectrometry

1995 ◽  
Vol 41 (1) ◽  
pp. 62-68 ◽  
Author(s):  
D H Chace ◽  
S L Hillman ◽  
D S Millington ◽  
S G Kahler ◽  
C R Roe ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Tandem Mass Spectrometry ◽  
Maple Syrup Urine Disease ◽  
Dried Blood Spots ◽  
Tandem Mass ◽  
Inhibition Assay ◽  
Maple Syrup ◽  
Blood Spots ◽  
Urine Disease ◽  
The Mean

Abstract We report a new method for the diagnosis of maple syrup urine disease (MSUD) from dried blood spots on newborn screening cards based on tandem mass spectrometry (MS-MS). The mean +/- SD concentration of Leu plus Ile in normal newborns was 151 +/- 47 mumol/L (n = 1096); for Val, 131 +/- 58 mumol/L (n = 791). SDs were lower when the concentrations of these amino acids were expressed relative to that of Phe. The mean ratio for Leu + Ile to Phe was 2.5 +/- 0.49; for Val to Phe, 2.18 +/- 0.51. These results compare well with values previously reported in the literature. With these criteria, samples from a collection categorized by a bacterial inhibition assay as normal or falsely positive for MSUD were normal by MS-MS [(Leu + Ile): Phe < 5.0]. Samples from confirmed MSUD patients were categorized as abnormal [(Leu+Ile): Phe > 9.0] by MS-MS.

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