The use of automated electrospray ionization tandem MS for the diagnosis of inborn errors of metabolism from dried blood spots

1996 ◽  
Vol 24 (3) ◽  
pp. 932-938 ◽  
Author(s):  
A. W. Johnson ◽  
K. Mills ◽  
P. T. Clayton
Keyword(s):  
Electrospray Ionization ◽  
Inborn Errors Of Metabolism ◽  
Dried Blood Spots ◽  
Tandem Ms ◽  
Inborn Errors ◽  
Blood Spots

scholarly journals Diagnostic potential of stored dried blood spots for inborn errors of metabolism: a metabolic autopsy of medium-chain acyl-CoA dehydrogenase deficiency

2018 ◽  
Vol 71 (10) ◽  
pp. 885-889 ◽  
Author(s):  
Noriyuki Kaku ◽  
Kenji Ihara ◽  
Yuichiro Hirata ◽  
Kenji Yamada ◽  
Sooyoung Lee ◽  
...  
Keyword(s):  
Newborn Screening ◽  
Inborn Errors Of Metabolism ◽  
Dried Blood Spots ◽  
Screening Tests ◽  
Inborn Errors ◽  
Mcad Deficiency ◽  
Medium Chain ◽  
Blood Spots ◽  
Chain Acyl ◽  
Biochemical Analyses

AimIt is estimated that 1–5% of sudden infant death syndrome (SIDS) cases might be caused by undiagnosed inborn errors of metabolism (IEMs); however, the postmortem identification of IEMs remains difficult. This study aimed to evaluate the usefulness of dried blood spots (DBSs) stored after newborn screening tests as a metabolic autopsy to determine the causes of death in infants and children who died suddenly and unexpectedly.MethodsInfants or toddlers who had suddenly died without a definite diagnosis between July 2008 and December 2012 at Kyushu University Hospital in Japan were enrolled in this study. Their Guthrie cards, which had been stored for several years at 4–8°C, were used for an acylcarnitine analysis by tandem mass spectrometry to identify inborn errors of metabolism.ResultsFifteen infants and children who died at less than 2 years of age and for whom the cause of death was unknown were enrolled for the study. After correcting the C0 and C8 values assuming the hydrolysation of acylcarnitine in the stored DBSs, the corrected C8 value of one case just exceeded the cut-off level for medium-chain acyl-CoA dehydrogenase (MCAD) deficiency screening. Genetic and biochemical analyses confirmed this patient to have MCAD deficiency.ConclusionDBSs stored after newborn screening tests are a promising tool for metabolic autopsy. The appropriate compensation of acylcarnitine data and subsequent genetic and biochemical analyses are essential for the postmortem diagnosis of inborn errors of metabolism.

scholarly journals QUALITY OF DRIED BLOOD SPOTS IS AN INTEGRAL COMPONENT OF PROMPT DETECTION OF INBORN ERRORS OF METABOLISM

2020 ◽  
Vol 10 (4(38)) ◽  
pp. 77-86
Author(s):  
Tetiana Znamenska ◽  
O. Vorobiova ◽  
I. Kuzneczov ◽  
I. Lastivka ◽  
A. Kremezna ◽  
...  
Keyword(s):  
Newborn Screening ◽  
Inborn Errors Of Metabolism ◽  
Dried Blood Spots ◽  
Poor Quality ◽  
Blood Sampling ◽  
Inborn Errors ◽  
Blood Spots ◽  
Expanded Newborn Screening ◽  
Practical Recommendations

Introduction. Inborn Errors of Metabolism (IEM) are constituted a group of genetic diseases that are associated with defects in the synthesis or catabolism of complex molecules, impaired intermediary metabolism and energy production/utilization processes. The clinical manifestation of IEM is nonspecific, that looks similar to septicemia, and most often occurs in the neonatal period with life-threatening acute metabolic crises. Expanded Newborn Screening (ENS) – a biochemical study of the blood of all newborns without exception with the purpose to identify molecular markers of these diseases proved to be the most effective instrument of early IEM diagnostics. The quality of the biological samples (dried blood spots, DBS) in great extent determines the timing, accuracy, and reliability of the results of biochemical measurements. Obtaining of equivocal results in the case of analysis of poor quality DBS requires repeated laboratory tests, that delays the diagnostic process and postpones the start of specific treatment, which usually results in irreversible damage of the brain and internal organs of the child. The aim of this work is to (i) review the first results of the implementation of Expanded Newborn Screening in Ukraine (pilot part of the Baby Screen Project), and to analyze literature data regarding the negative impact of poor quality DBS on laboratory determination of IEM marker substances contents in the specimens, (ii) to characterize the typical errors in blood sampling and drying of  blood spots, and (iii) to provide practical recommendations for the proper performance of these procedures. Materials and methods. Own data of retrospective analysis of the questionable ENS results was superimposed with dried blood specimens, that were investigated in the Pharmbiotest ENS Lab to outline most common inaccuracies. Based on the comparison of these data with the relevant publications it was formulated the practical recommendations for improving quality of DBS preparation to ensure the accuracy and reliability of laboratory measurements and speed up IEM diagnostics. Results. The quality of biomaterial selection is an important part of obtaining reliable results during expanded newborn screening. Capillary blood is collected in the maternity hospital from 48-72 hours (full-term) and for 7-11 days (in preterm babies) after the birth from the heel of babies. In this case, a few drops of blood are applied to a special test card made of filter paper, which is dried and sent to the laboratory. Blood tests are performed using a highly sensitive and accurate method of chemical analysis - tandem mass spectrometry in the laboratory "Pharmbiotest", located in Ukraine. Taking into analysis the low-quality samples lead to questionable results, which requires repeated DBS sampling and re-examining. This proved to be the most common cause of delaying IEM detection, diagnosis establishment, and initiation of treatment, which can be fatal for a child with severe IEM forms. Conclusions. Informing healthcare professionals and parents about the current results of laboratory monitoring of dried blood spots quality, typical errors in blood sampling and following on-site procedures and negative consequences of its improper performance, as well as providing clear practical recommendations of how these procedures should be done is a proven way of improving and speeding up IEM diagnostics.

scholarly journals Instability of Acylcarnitines in Stored Dried Blood Spots: The Impact on Retrospective Analysis of Biomarkers for Inborn Errors of Metabolism

2020 ◽  
Vol 6 (4) ◽  
pp. 83
Author(s):  
Willemijn J. van Rijt ◽  
Peter C. J. I. Schielen ◽  
Yasemin Özer ◽  
Klaas Bijsterveld ◽  
Fjodor H. van der Sluijs ◽  
...  
Keyword(s):  
Validation Studies ◽  
Inborn Errors Of Metabolism ◽  
Room Temperature ◽  
Dried Blood Spots ◽  
Positive Trend ◽  
Inborn Errors ◽  
Retrospective Diagnosis ◽  
Screening Programs ◽  
Blood Spots ◽  
The Impact

Stored dried blood spots (DBS) can provide valuable samples for the retrospective diagnosis of inborn errors of metabolism, and for validation studies for newborn blood spot screening programs. Acylcarnitine species are subject to degradation upon long-term storage at room temperature, but limited data are available on the stability in original samples and the impact on acylcarnitine ratios. We analysed complete acylcarnitine profiles by flow-injection tandem mass spectrometry in 598 anonymous DBS stored from 2013 to 2017, at +4 °C during the first year and thereafter at room temperature. The concentrations of C2-, C3-, C4-, C5-, C6-, C8-, C10:1-, C10-, C12:1-, C12-, C14:1-, C14-, C16:1-, C16-, C18:2-, C18:1-, C18-, C5OH+C4DC-, C18:1OH-, and C16DC-carnitine decreased significantly, whereas a positive trend was found for free carnitine. Only the C4/C8-, C8/C10-, C14:1/C10- and C14:1/C16-carnitine ratios appeared robust for the metabolite instability. The metabolite instability may provoke the wrong interpretation of test results in the case of retrospective studies and risk the inaccurate estimation of cut-off targets in validation studies when only stored control DBS are used. We recommend including control DBS in diagnostic, retrospective cohort studies, and, for validation studies, we recommend using fresh samples and repeatedly re-evaluating cut-off targets.

Simultaneous determination of cocaine and opiates in dried blood spots by electrospray ionization tandem mass spectrometry

Talanta ◽  
2013 ◽  
Vol 117 ◽  
pp. 235-241 ◽  
Author(s):  
Ángel Antelo-Domínguez ◽  
José Ángel Cocho ◽  
María Jesús Tabernero ◽  
Ana María Bermejo ◽  
Pilar Bermejo-Barrera ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Tandem Mass Spectrometry ◽  
Electrospray Ionization ◽  
Simultaneous Determination ◽  
Dried Blood Spots ◽  
Tandem Mass ◽  
Blood Spots ◽  
Ionization Tandem Mass Spectrometry

Contamination of dried blood spots – an underestimated risk in newborn screening

2018 ◽  
Vol 56 (2) ◽  
pp. 278-284 ◽  
Author(s):  
Theresa Winter ◽  
Anja Lange ◽  
Anke Hannemann ◽  
Matthias Nauck ◽  
Cornelia Müller
Keyword(s):  
Newborn Screening ◽  
Infant Formula ◽  
False Positive ◽  
Dried Blood Spots ◽  
Substantial Effect ◽  
Blood Collection ◽  
Inborn Errors ◽  
Blood Spots ◽  
Filter Papers ◽  
The Impact

Abstract Background: Newborn screening (NBS) is an established screening procedure in many countries worldwide, aiming at the early detection of inborn errors of metabolism. For decades, dried blood spots have been the standard specimen for NBS. The procedure of blood collection is well described and standardized and includes many critical pre-analytical steps. We examined the impact of contamination of some anticipated common substances on NBS results obtained from dry spot samples. This possible pre-analytical source of uncertainty has been poorly examined in the past. Methods: Capillary blood was obtained from 15 adult volunteers and applied to 10 screening filter papers per volunteer. Nine filter papers were contaminated without visible trace. The contaminants were baby diaper rash cream, baby wet wipes, disinfectant, liquid infant formula, liquid infant formula hypoallergenic (HA), ultrasonic gel, breast milk, feces, and urine. The differences between control and contaminated samples were evaluated for 45 NBS quantities. We estimated if the contaminations might lead to false-positive NBS results. Results: Eight of nine investigated contaminants significantly altered NBS analyte concentrations and potentially caused false-positive screening outcomes. A contamination with feces was most influential, affecting 24 of 45 tested analytes followed by liquid infant formula (HA) and urine, affecting 19 and 13 of 45 analytes, respectively. Conclusions: A contamination of filter paper samples can have a substantial effect on the NBS results. Our results underline the importance of good pre-analytical training to make the staff aware of the threat and ensure reliable screening results.

scholarly journals Monitoring of Congenital Adrenal Hyperplasia by Microbore HPLC–Electrospray Ionization Tandem Mass Spectrometry of Dried Blood Spots

2002 ◽  
Vol 48 (2) ◽  
pp. 354-356 ◽  
Author(s):  
Chien-Chen Lai ◽  
Chang-Hai Tsai ◽  
Fuu-Jen Tsai ◽  
Jer-Yuarn Wu ◽  
Wei-De Lin ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Tandem Mass Spectrometry ◽  
Congenital Adrenal Hyperplasia ◽  
Electrospray Ionization ◽  
Dried Blood Spots ◽  
Tandem Mass ◽  
Adrenal Hyperplasia ◽  
Blood Spots ◽  
Ionization Tandem Mass Spectrometry

Protein-dependent inborn errors of metabolism

2020 ◽  
pp. 1942-1984
Author(s):  
Georg F. Hoffmann ◽  
Stefan Kölker
Keyword(s):  
Amino Acids ◽  
Organic Acid ◽  
Inborn Errors Of Metabolism ◽  
Intracellular Transport ◽  
Metabolic Diseases ◽  
Dried Blood Spots ◽  
Distinct Pattern ◽  
Inborn Errors ◽  
Enzyme Defects ◽  
Specific Disorders

Protein-dependent inborn errors of metabolism are caused by inherited enzyme defects of catabolic pathways or intracellular transport of amino acids. Most result in an accumulation of metabolites upstream of the defective enzyme (amino acids and/or ammonia), causing intoxication. Protein-dependent metabolic diseases usually have a low prevalence except for some high-risk communities with high consanguinity rates. However, the cumulative prevalence of these disorders is considerable (i.e. at least >1:2000 newborns) and represents an important challenge for all public health systems. Types and clinical presentation of protein-dependent inborn errors of metabolism—this chapter discusses amino acid disorders, organic acid disorders, and urea cycle defects. The disease spectrum is broad, but follows a distinct pattern in specific disorders. Investigation and management—every infant presenting with symptoms of unexplained metabolic crisis, intoxication, or encephalopathy requires urgent evaluation of metabolic parameters, including analyses of arterial blood gases, serum glucose and lactate, plasma ammonia and amino acids, acylcarnitine profiling in dried blood spots, and organic acid analysis in urine. This chapter discusses the basic principles of acute emergency therapy and of long-term treatment, which aims principally to mitigate the metabolic consequences of enzyme deficiencies by compensating for them. Successful treatment of affected individuals is often difficult to achieve. Careful supervision in metabolic centres involving an experienced multidisciplinary team is invaluable for the best outcome.

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