scholarly journals Age-Related Variations in Acylcarnitine and Free Carnitine Concentrations Measured by Tandem Mass Spectrometry

2005 ◽  
Vol 51 (4) ◽  
pp. 745-752 ◽  
Author(s):  
Catia Testa Cavedon ◽  
Pierre Bourdoux ◽  
Karl Mertens ◽  
Hong Vien Van Thi ◽  
Nadine Herremans ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Tandem Mass Spectrometry ◽  
Cord Blood ◽  
Reference Values ◽  
Free Carnitine ◽  
Control Group ◽  
Tandem Mass ◽  
Older Children ◽  
Blood Spots ◽  
Age Related

Abstract Background: The acylcarnitine profiles obtained from dried blood spots on “Guthrie cards” have been widely used for the diagnosis and follow-up of children suspected of carrying an inherited error of metabolism, but little attention has been paid to potential age-related variations in the reference values. In this study, we evaluated the variations in free carnitine and acylcarnitine concentrations with age, as measured by tandem mass spectrometry. Methods: Filter-paper blood spots were collected from 433 healthy individuals over a period of 17 months. Eight age groups were defined: cord blood, 3–6 days (control group), 15–55 days, 2–18 months, 19–59 months, 5–10 years, 11–17 years, and 18–54 years. Free carnitine and acylcarnitines were measured for each individual. Mean values were calculated for each age group and compared with those for the control group. Results: Free carnitine was significantly higher in older children than in newborns (P <0.05), but the concentrations of several acylcarnitines tended to be significantly lower in cord blood and in groups of older children than in the control group. Only minor sex-related differences were observed. Conclusion: Although the risk of underdiagnosis of fatty acid oxidation disorders with the use of newborn values as reference can be considered as small, in some circumstances the use of age-related reference values may have a potential impact on the diagnosis and management of inherited errors of metabolism.

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.

scholarly journals Rapid diagnosis of MCAD deficiency: quantitative analysis of octanoylcarnitine and other acylcarnitines in newborn blood spots by tandem mass spectrometry

1997 ◽  
Vol 43 (11) ◽  
pp. 2106-2113 ◽  
Author(s):  
Donald H Chace ◽  
Steven L Hillman ◽  
Johan L K Van Hove ◽  
Edwin W Naylor
Keyword(s):  
Mass Spectrometry ◽  
Tandem Mass Spectrometry ◽  
Newborn Screening ◽  
Chain Length ◽  
Filter Paper ◽  
Tandem Mass ◽  
Mcad Deficiency ◽  
Medium Chain ◽  
Blood Spots ◽  
Medium Chain Length

Abstract We report the application of tandem mass spectrometry to prospective newborn screening for medium-chain acyl-CoA dehydrogenase (MCAD) deficiency. MCAD deficiency is diagnosed from dried blood spots on filter paper cards from newborns on the basis of the increase of medium chain length acylcarnitines identified by isotope dilution mass spectrometry methods. A robust and accurate semiautomated method for the analysis of medium chain length acylcarnitines as their butyl esters was developed and validated. Quantitative data from the analyses of 113 randomly collected filter paper blood spots from healthy newborns showed low concentrations of medium chain length acylcarnitines such as octanoylcarnitine. The maximum concentration of octanoylcarnitine was 0.22 μmol/L, with the majority being at or below the detection limit. In all 16 blood spots from newborns with confirmed MCAD deficiency, octanoylcarnitine was highly increased [median 8.4 μmol/L (range 3.1–28.3 μmol/L)], allowing easy detection. The concentration of octanoylcarnitine was significantly higher in these 16 newborns (<3 days of age) than in 16 older patients (ages 8 days to 7 years) with MCAD deficiency (median 1.57 μmol/L, range 0.33–4.4). The combined experience of prospective newborn screening in Pennsylvania and North Carolina has shown a disease frequency for MCAD deficiency of 1 in 17 706. No false-positive and no known false-negative results have been found. A validated method now exists for prospective newborn screening for MCAD deficiency.

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
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