ArticleJIMD reports2016
The Newborn Screening Paradox: Sensitivity vs. Overdiagnosis in VLCAD Deficiency.
Article in JIMD reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 17 citations in OpenAlex.
- Long-Chain Fatty Acid Oxidation Disorder Genes: A Comprehensive Genetic Database of LC-FAOD Variants, Genotypes, and Phenotypes.Human mutation · 2026Article
- Characteristic Findings of Infants with Transient Elevation of Acylcarnitines in Neonatal Screening and Neonatal Weight Loss.International journal of neonatal screening · 2025Article
- Insights from the Newborn Screening Program for Very Long-Chain Acyl-CoA Dehydrogenase (VLCAD) Deficiency in Kuwait.International journal of neonatal screening · 2025Article
- Using the C14:1/Medium-Chain Acylcarnitine Ratio Instead of C14:1 to Reduce False-Positive Results for Very-Long-Chain Acyl-CoA Dehydrogenase Deficiency in Newborn Screening in Japan.International journal of neonatal screening · 2024Article
- Specifications of the ACMG/AMP guidelines for ACADVL variant interpretation.Molecular genetics and metabolism · 2023Article
- New Acylcarnitine Ratio as a Reliable Indicator of Long-Chain 3-Hydroxyacyl-CoA Dehydrogenase Deficiency.International journal of neonatal screening · 2023Article
- Severity estimation of very-long-chain acyl-CoA dehydrogenase deficiency viaPediatric research · 2022Article
- Estimating the Prevalence of Rare Diseases: Long-Chain Fatty Acid Oxidation Disorders as an Illustrative Example.Advances in therapy · 2022Article
- Abnormal VLCADD newborn screening resembling MADD in four neonates with decreased riboflavin levels and VLCAD activity.JIMD reports · 2021Article
- Electrophysiological Abnormalities in VLCAD Deficient hiPSC-Cardiomyocytes Can Be Improved by Lowering Accumulation of Fatty Acid Oxidation Intermediates.International journal of molecular sciences · 2020Article
- Reducing False-Positive Results in Newborn Screening Using Machine Learning.International journal of neonatal screening · 2020Article
- The diagnostic challenge in very-long chain acyl-CoA dehydrogenase deficiency (VLCADD).Journal of inherited metabolic disease · 2018Article
- Follow-up status during the first 5 years of life for metabolic disorders on the federal Recommended Uniform Screening Panel.Genetics in medicine : official journal of the American College of Medical Genetics · 2018Article
- Disorders of mitochondrial long-chain fatty acid oxidation and the carnitine shuttle.Reviews in endocrine & metabolic disorders · 2018Review
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Authors and funding
9 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveTo improve the efficacy of newborn screening (NBS) for very long chain acyl-CoA dehydrogenase deficiency (VLCADD). PATIENTS AND
methodsData on all dried blood spots collected by the Dutch NBS from October 2007 to 2010 (742.728) were included. Based solely on the C14:1 levels (cutoff ≥0.8 μmol/L), six newborns with VLCADD had been identified through NBS during this period. The ratio of C14:1 over C2 was calculated. DNA of all blood spots with a C14:1/C2 ratio of ≥0.020 was isolated and sequenced. Children homozygous or compound heterozygous for mutations in the ACADVL gene were traced back and invited for detailed clinical, biochemical, and genetic evaluation.
resultsRetrospective analysis based on the C14:1/C2 ratio with a cutoff of ≥0.020 identified an additional five children with known ACADVL mutations and low enzymatic activity. All were still asymptomatic at the time of diagnosis (age 2-5 years). Increasing the cutoff to ≥0.023 resulted in a sensitivity of 93% and a positive predictive value of 37%. The sensitivity of the previously used screening approach (C14:1 ≥0.8) was 50%.
conclusionThis study shows that the ratio C14:1/C2 is a more sensitive marker than C14:1 for identifying VLCADD patients in NBS. However, as these patients were all asymptomatic at the time of diagnosis, this suggests that a more sensitive screening approach may also identify individuals who may never develop clinical disease. Long-term follow-up studies are needed to establish the risk of these VLCADD-deficient individuals for developing clinical signs and symptoms.
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