Trace elements in dried blood spots as potential discriminating features for metabolic disorders diagnosis in new-borns

Abstract Trace elements in dried blood spots (DBS) from new-born were determined by laser ablation (LA) coupled with inductively coupled mass spectrometry (ICP-MS), and data was subjected to chemometric evaluation in an attempt to classify healthy new-born and new-born suffering metabolic disorders. Unsupervised [principal component analysis (PCA), and cluster analysis (CA)], and supervised [linear discriminant analysis (LDA), and soft independent modelling by class analogy (SIMCA)] pattern recognition techniques were used as classification techniques. PCA and CA have shown a clear tendency to form two groups (healthy and new-born suffering metabolic disorders). LDA and SIMCA have predicted that 90.5 and 83.9% of original grouped healthy new-born cases were correctly classified by LDA and SIMCA, respectively. In addition, these percentages were 97.6% (LDA) and 80.6% (SIMCA) for DBSs from new-born suffering metabolic disorders. However, SIMCA has only detected one misclassified DBS from the healthy group, and the lower percentage is attributed to four DBDs from healthy new-borns group and five DBSs from new-borns with disorders which were found to be as belonging to both categories (healthy new-borns and new-borns with disorders) in the training set. LDA also gave a % of grouped maple syrup urine disease (MSUD) cases correctly classified of 100%, although the percentage fells to 66.7% when classifying phenylketonuria (PKU) cases. Finally, essential elements such as Fe, K, Rb, and Zn were found to be matched (correlated) with the concentration of amino acids such as phenylalanine, valine and leucine, biomarkers linked with MSUD and PKU diseases.

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Second-Tier Test for Quantification of Alloisoleucine and Branched-Chain Amino Acids in Dried Blood Spots to Improve Newborn Screening for Maple Syrup Urine Disease (MSUD)

Clinical Chemistry ◽

10.1373/clinchem.2007.098434 ◽

2008 ◽

Vol 54 (3) ◽

pp. 542-549 ◽

Cited By ~ 65

Author(s):

Devin Oglesbee ◽

Karen A Sanders ◽

Jean M Lacey ◽

Mark J Magera ◽

Bruno Casetta ◽

...

Keyword(s):

Amino Acids ◽

Newborn Screening ◽

Dried Blood Spots ◽

Branched Chain Amino Acids ◽

Maple Syrup ◽

Blood Spots ◽

Urine Disease ◽

Second Tier ◽

Branched Chain ◽

Positive Results

Abstract Background: Newborn screening for maple syrup urine disease (MSUD) relies on finding increased concentrations of the branched-chain amino acids (BCAAs) leucine, isoleucine, and valine by tandem mass spectrometry (MS/MS). d-Alloisoleucine (allo-Ile) is the only pathognomonic marker of MSUD, but it cannot be identified by existing screening methods because it is not differentiated from isobaric amino acids. Furthermore, newborns receiving total parenteral nutrition often have increased concentrations of BCAAs. To improve the specificity of newborn screening for MSUD and to reduce the number of diet-related false-positive results, we developed a LC-MS/MS method for quantifying allo-Ile. Methods: Allo-Ile and other BCAAs were extracted from a 3/16-inch dried blood spot punch with methanol/H2O, dried under nitrogen, and reconstituted into mobile phase. Quantitative LC-MS/MS analysis of allo-Ile, its isomers, and isotopically labeled internal standards was achieved within 15 min. To determine a reference interval for BCAAs including allo-Ile, we analyzed 541 dried blood spots. We also measured allo-Ile in blinded samples from 16 MSUD patients and 21 controls and compared results to an HPLC method. Results: Intra- and interassay imprecision (mean CVs) for allo-Ile, leucine, isoleucine, and valine ranged from 1.8% to 7.4%, and recovery ranged from 91% to 129%. All 16 MSUD patients were correctly identified. Conclusions: The LC-MS/MS method can reliably measure allo-Ile in dried blood spots for the diagnosis of MSUD. Applied to newborn screening as a second-tier test, it will reduce false-positive results, which produce family anxiety and increase follow-up costs. The assay also appears suitable for use in monitoring treatment of MSUD patients.

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Short-Term Stability of Amino acids and Acylcarnitines in the Dried Blood Spots Used to Screen Newborns for Metabolic Disorders

Journal of Medical Screening ◽

10.1177/0969141314525367 ◽

2014 ◽

Vol 21 (1) ◽

pp. 5-9 ◽

Cited By ~ 12

Author(s):

J Golbahar ◽

DD Altayab ◽

E Carreon

Keyword(s):

Amino Acids ◽

Metabolic Disorders ◽

Dried Blood Spots ◽

Short Term ◽

Term Stability ◽

Blood Spots

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

Clinical Chemistry ◽

10.1093/clinchem/41.1.62 ◽

1995 ◽

Vol 41 (1) ◽

pp. 62-68 ◽

Cited By ~ 148

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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ICP-MS Assessment of Essential and Toxic Trace Elements in Foodstuffs with Different Geographic Origins Available in Romanian Supermarkets

Molecules ◽

10.3390/molecules26237081 ◽

2021 ◽

Vol 26 (23) ◽

pp. 7081

Author(s):

Cezara Voica ◽

Constantin Nechita ◽

Andreea Maria Iordache ◽

Carmen Roba ◽

Ramona Zgavarogea ◽

...

Keyword(s):

Trace Elements ◽

Inductively Coupled Plasma ◽

Hazard Quotient ◽

Risk Index ◽

Daily Intake ◽

Principal Component ◽

Hierarchical Cluster ◽

Essential Elements ◽

Target Hazard Quotient ◽

Toxic Trace Elements

The present study was conducted to quantify the daily intake and target hazard quotient of four essential elements, namely, chromium, cobalt, nickel, and copper, and four toxic trace elements, mercury, cadmium, lead, and arsenic. Thirty food items were assigned to five food categories (seeds, leaves, powders, beans, and fruits) and analyzed using inductively coupled plasma-mass spectrometry. Factor analysis after principal component extraction revealed common metal patterns in all foodstuffs, and using hierarchical cluster analysis, an association map was created to illustrate their similarity. The results indicate that the internationally recommended dietary allowance was exceeded for Cu and Cr in 27 and 29 foodstuffs, respectively. According to the tolerable upper level for Ni and Cu, everyday consumption of these elements through repeated consumption of seeds (fennel, opium poppy, and cannabis) and fruits (almond) can have adverse health effects. Moreover, a robust correlation between Cu and As (p < 0.001) was established when all samples were analyzed. Principal component analysis (PCA) demonstrated an association between Pb, As, Co, and Ni in one group and Cr, Cu, Hg, and Cd in a second group, comprising 56.85% of the total variance. For all elements investigated, the cancer risk index was within safe limits, highlighting that lifetime consumption does not increase the risk of carcinogens.

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