ArticlePloS one2017
Simultaneous determination of 3-hydroxypropionic acid, methylmalonic acid and methylcitric acid in dried blood spots: Second-tier LC-MS/MS assay for newborn screening of propionic acidemia, methylmalonic acidemias and combined remethylation disorders.
Article in PloS one, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
27 citing papers in PubMed, 64 citations in OpenAlex.
- Too Early to Tell? Balancing Diagnostic Accuracy of Newborn Screening for Propionic Acidemia Versus a Timely Referral.International journal of neonatal screening · 2025Article
- Ancestral Sequence Reconstruction of the Ethylene-Forming Enzyme.Biochemistry · 2025Article
- Biochemical, Structural, and Conformational Characterization of a Fungal Ethylene-Forming Enzyme.Biochemistry · 2025Article
- Digital-Tier Strategy Improves Newborn Screening for Glutaric Aciduria Type 1.International journal of neonatal screening · 2024Article
- The utility of methylmalonic acid, methylcitrate acid, and homocysteine in dried blood spots for therapeutic monitoring of three inherited metabolic diseases.Frontiers in nutrition · 2024Article
- Combined Newborn Screening Allows Comprehensive Identification also of Attenuated Phenotypes for Methylmalonic Acidurias and Homocystinuria.Nutrients · 2023Article
- Biomarkers to predict disease progression and therapeutic response in isolated methylmalonic acidemia.Journal of inherited metabolic disease · 2023Review
- Review
- Maternal Vitamin BNutrients · 2022Article
- Opportunities and challenges in machine learning-based newborn screening-A systematic literature review.JIMD reports · 2022Article
- Second-tier strategies in newborn screening - potential and limitations.Medizinische Genetik : Mitteilungsblatt des Berufsverbandes Medizinische Genetik e.V · 2022Article
- Biomarkers for drug development in propionic and methylmalonic acidemias.Journal of inherited metabolic disease · 2022Review
- Screening for Methylmalonic and Propionic Acidemia: Clinical Outcomes and Follow-Up Recommendations.International journal of neonatal screening · 2022Article
- Application of the Artificial Intelligence Algorithm Model for Screening of Inborn Errors of Metabolism.Frontiers in pediatrics · 2022Article
- The Editor's Choice for Issue 3, Volume 7.International journal of neonatal screening · 2021Article
- Development of Second-Tier Liquid Chromatography-Tandem Mass Spectrometry Analysis for Expanded Newborn Screening in Japan.International journal of neonatal screening · 2021Article
- Maternal vitamin deficiency mimicking multiple acyl-CoA dehydrogenase deficiency on newborn screening.Molecular genetics and metabolism reports · 2021Article
- Implementation of second-tier tests in newborn screening for the detection of vitamin BOrphanet journal of rare diseases · 2021Article
- Analysis of 2-methylcitric acid, methylmalonic acid, and total homocysteine in dried blood spots by LC-MS/MS for application in the newborn screening laboratory: A dual derivatization approach.Journal of mass spectrometry and advances in the clinical lab · 2021Article
- Partial Biotinidase Deficiency Revealed Imbalances in Acylcarnitines Profile at Tandem Mass Spectrometry Newborn Screening.International journal of environmental research and public health · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
BACKGROUND AND
aimsIncreased propionylcarnitine levels in newborn screening are indicative for a group of potentially severe disorders including propionic acidemia (PA), methylmalonic acidemias and combined remethylation disorders (MMACBL). This alteration is relatively non-specific, resulting in the necessity of confirmation and differential diagnosis in subsequent tests. Thus, we aimed to develop a multiplex approach for concurrent determination of 3-hydroxypropionic acid, methylmalonic acid and methylcitric acid from the same dried blood spot (DBS) as in primary screening (second-tier test). We also set out to validate the method using newborn and follow-up samples of patients with confirmed PA or MMACBL.
methodsThe assay was developed using liquid chromatography-tandem mass spectrometry and clinically validated with retrospective analysis of DBS samples from PA or MMACBL patients.
resultsReliable determination of all three analytes in DBSs was achieved following simple and fast (<20 min) sample preparation without laborious derivatization or any additional pipetting steps. The method clearly distinguished the pathological and normal samples and differentiated between PA and MMACBL in all stored newborn specimens. Methylcitric acid was elevated in all PA samples; 3-hydroxypropionic acid was also high in most cases. Methylmalonic acid was increased in all MMACBL specimens; mostly together with methylcitric acid.
conclusionsA liquid chromatography-tandem mass spectrometry assay allowing simultaneous determination of the biomarkers 3-hydroxypropionic acid, methylmalonic acid and methylcitric acid in DBSs has been developed. The assay can use the same specimen as in primary screening (second-tier test) which may reduce the need for repeated blood sampling. The presented preliminary findings suggest that this method can reliably differentiate patients with PA and MMACBL in newborn screening. The validated assay is being evaluated prospectively in a pilot project for extension of the German newborn screening panel (‟Newborn screening 2020"; Newborn Screening Center, University Hospital Heidelberg).
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.