ArticleJIMD reports2020
A newborn screening approach to diagnose 3-hydroxy-3-methylglutaryl-CoA lyase deficiency.
Article in JIMD reports, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers, 1 of them a synthesis that pooled it.
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Who cites it
7 citing papers in PubMed, 1 synthesis or guideline pooled it, 20 citations in OpenAlex.
- Evaluation of Newborn Screening for Diseases Using C5-OH as a Marker: Systematic Review of the Literature and Evaluation of 17 Years of C5-OH Screening in the Netherlands.Journal of inherited metabolic disease · 2025Pooled it
- Timely intervention in HMG-CoA Lyase deficiency: The role of newborn screening, metabolic management, and genomic sequencing.Molecular genetics and metabolism reports · 2025Article
- Newborn screening and genetic diagnosis of 3-methylcrotonyl-CoA carboxylase deficiency in Quanzhou,China.Molecular genetics and metabolism reports · 2024Article
- Metabolic Pathways of Acylcarnitine Synthesis.Physiological research · 2024Review
- Diagnosis of inborn errors of metabolism within the expanded newborn screening in the Madrid region.JIMD reports · 2022Article
- HMG-CoA Lyase Deficiency: A Retrospective Study of 62 Saudi Patients.Frontiers in genetics · 2022Article
- A newborn screening approach to diagnose 3-hydroxy-3-methylglutaryl-CoA lyase deficiency.JIMD reports · 2020Article
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Authors and funding
16 authors at 6 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
3-Hydroxy-3-methylglutaryl-coenzyme A lyase deficiency (HMGCLD) is a rare autosomal recessively inherited metabolic disorder. Patients suffer from avoidable neurologically devastating metabolic decompensations and thus would benefit from newborn screening (NBS). The diagnosis is currently made by measuring dry blood spot acylcarnitines (C5OH and C6DC) followed by urinary organic acid profiling for the differential diagnosis from several other disorders. Using untargeted metabolomics (reversed-phase UHPLC coupled to an Orbitrap Elite hybrid mass spectrometer) of plasma samples from 5 HMGCLD patients and 19 age-matched controls, we found 3-methylglutaconic acid and 3-hydroxy-3-methylglutaric acid, together with 3-hydroxyisovalerylcarnitine as the most discriminating metabolites between the groups. In order to evaluate the NBS potential of these metabolites we quantified the most discriminating metabolites from untargeted metabolomics in 23 blood spots from 4 HMGCLD patients and 55 controls by UHPLC tandem mass spectrometry. The results provide a tool for expanded NBS of HMGCLD using tandem mass spectrometry. Selected reaction monitoring transition 262/85 could be used in a first-tier NBS analysis to screen for elevated 3-hydroxyisovalerylcarnitine. In a positive case, a second-tier analysis of 3-hydroxy-3-methylglutaric acid and 3-methylglutaconic acid in a dry blood spot using UHPLC tandem mass spectrometry instruments confirms the diagnosis. In conclusion, we describe the identification of new diagnostic biomarkers for HMGCLD and their application in NBS in dry blood spots. By using second-tier testing, all patients with HMGCLD were unequivocally and correctly diagnosed.
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