ArticleGenetics in medicine : official journal of the American College of Medical Genetics2019
Combining newborn metabolic and DNA analysis for second-tier testing of methylmalonic acidemia.
Article in Genetics in medicine : official journal of the American College of Medical Genetics, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers, 1 of them a synthesis that pooled it.
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
31 citing papers in PubMed, 1 synthesis or guideline pooled it, 44 citations in OpenAlex.
- Systematic literature review and meta-analysis on the epidemiology of methylmalonic acidemia (MMA) with a focus on MMA caused by methylmalonyl-CoA mutase (mut) deficiency.Orphanet journal of rare diseases · 2019Pooled it
- Second-tier genetics improves newborn screening accuracy for SCID and other T cell deficiencies.Journal of human immunity · 2026Article
- Revolutionizing neonatal health: India's journey from assays to advanced genetics.Journal of applied genetics · 2026Review
- Historical Perspectives, Classification and Diagnostic Approaches of Inborn Errors of Metabolism: A Systematic Review and Meta-Analysis.Metabolites · 2026Review
- Improving newborn screening accuracy through genome sequencing, targeted metabolomics, and machine learning.BMC medical genomics · 2025Article
- Next-generation Sequencing and Other Second Tier Tests in Newborn Screening for (X-linked) Agammaglobulinemia.Journal of clinical immunology · 2025Article
- CFTR haplotype phasing using long-read genome sequencing from ultralow input DNA.Genetics in medicine open · 2025Article
- Improving methylmalonic acidemia (MMA) screening and MMA genotype prediction using random forest classifier in two Chinese populations.European journal of medical research · 2024Article
- Improving the second-tier classification of methylmalonic acidemia patients using a machine learning ensemble method.World journal of pediatrics : WJP · 2024Article
- Incorporating Next-Generation Sequencing as a Second-Tier Test for Primary Carnitine Deficiency.Molecular genetics & genomic medicine · 2024Article
- Harnessing Next-Generation Sequencing as a Timely and Accurate Second-Tier Screening Test for Newborn Screening of Inborn Errors of Metabolism.International journal of neonatal screening · 2024Article
- Using metabolic abnormalities of carriers in the neonatal period to evaluate the pathogenicity of variants of uncertain significance in methylmalonic acidemia.Frontiers in genetics · 2024Article
- Newborn Genetic Screening-Still a Role for Sanger Sequencing in the Era of NGS.International journal of neonatal screening · 2023Article
- dbRUSP: An Interactive Database to Investigate Inborn Metabolic Differences for Improved Genetic Disease Screening.International journal of neonatal screening · 2022Article
- Opportunities and challenges in machine learning-based newborn screening-A systematic literature review.JIMD reports · 2022Article
- Probing the functional consequence and clinical relevance of CD320 p.E88del, a variant in the transcobalamin receptor gene.American journal of medical genetics. Part A · 2022Article
- Application of a next-generation sequencing (NGS) panel in newborn screening efficiently identifies inborn disorders of neonates.Orphanet journal of rare diseases · 2022Article
- Computational approaches for predicting variant impact: An overview from resources, principles to applications.Frontiers in genetics · 2022Review
- The Editor's Choice for Issue 3, Volume 7.International journal of neonatal screening · 2021Article
- A rare mutation c.1663G > A (p.A555T) in the MMUT gene associated with mild clinical and biochemical phenotypes of methylmalonic acidemia in 30 Chinese patients.Orphanet journal of rare diseases · 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
11 authors at 3 institutions in 1 country.
Funding
Abstract
purposeImproved second-tier tools are needed to reduce false-positive outcomes in newborn screening (NBS) for inborn metabolic disorders on the Recommended Universal Screening Panel (RUSP).
methodsWe designed an assay for multiplex sequencing of 72 metabolic genes (RUSPseq) from newborn dried blood spots. Analytical and clinical performance was evaluated in 60 screen-positive newborns for methylmalonic acidemia (MMA) reported by the California Department of Public Health NBS program. Additionally, we trained a Random Forest machine learning classifier on NBS data to improve prediction of true and false-positive MMA cases.
resultsOf 28 MMA patients sequenced, we found two pathogenic or likely pathogenic (P/LP) variants in a MMA-related gene in 24 patients, and one pathogenic variant and a variant of unknown significance (VUS) in 1 patient. No such variant combinations were detected in MMA false positives and healthy controls. Random Forest-based analysis of the entire NBS metabolic profile correctly identified the MMA patients and reduced MMA false-positive cases by 51%. MMA screen-positive newborns were more likely of Hispanic ethnicity.
conclusionOur two-pronged approach reduced false positives by half and provided a reportable molecular finding for 89% of MMA patients. Challenges remain in newborn metabolic screening and DNA variant interpretation in diverse multiethnic populations.
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.