ReviewMolecular genetics and metabolism2017
Lethal neonatal case and review of primary short-chain enoyl-CoA hydratase (SCEH) deficiency associated with secondary lymphocyte pyruvate dehydrogenase complex (PDC) deficiency.
Review in Molecular genetics and metabolism, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03056794 (Natural History and Advanced Genetic Study of Pyruvate Dehydrogenase Complex Deficiencies), which is not on this map. Cited by 29 papers, 1 of them a synthesis that pooled it.
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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.
Natural History and Advanced Genetic Study of Pyruvate Dehydrogenase Complex Deficiencies (North American Mitochondrial Disease Consortium, Rare Diseases Clinical Research Network, Project 7413)
Who cites it
29 citing papers in PubMed, 1 synthesis or guideline pooled it, 45 citations in OpenAlex.
- Short-chain enoyl-CoA hydratase deficiency: a systematic review of clinical spectrum, genotype-phenotype correlations and survival predictors.Neurogenetics · 2026Pooled it
- Consensus Guidelines for Diagnosis and Management of Pyruvate Dehydrogenase Complex Deficiency.Journal of inherited metabolic disease · 2026Review
- Article
- Structural and biochemical mechanism of short-chain enoyl-CoA hydratase (ECHS1) substrate recognition.Communications biology · 2025Article
- A missense mutation in PDHB gene: identification of the patient with pyruvate dehydrogenase deficiency and demonstration of pathogenicity in vitro.Italian journal of pediatrics · 2025Article
- Neurological, metabolic and inflammatory phenotypes in a mouse model of ECHS1 deficiency.Brain communications · 2025Article
- Whole exome sequencing in energy deficiency inborn errors of metabolism: A systematic review.Molecular genetics and metabolism reports · 2024Review
- Valine and Inflammation Drive Epilepsy in a Mouse Model of ECHS1 Deficiency.bioRxiv : the preprint server for biology · 2024Article
- Loss of mitochondrial fatty acid β-oxidation protein short-chain Enoyl-CoA hydratase disrupts oxidative phosphorylation protein complex stability and function.The FEBS journal · 2023Article
- Clinical improvements after treatment with a low-valine and low-fat diet in a pediatric patient with enoyl-CoA hydratase, short chain 1 (ECHS1) deficiency.Orphanet journal of rare diseases · 2022Article
- Solvent accessibility of E1α and E1β residues with known missense mutations causing pyruvate dehydrogenase complex (PDC) deficiency: Impact on PDC-E1 structure and function.Journal of inherited metabolic disease · 2022Article
- Nicotinamide Mononucleotide Alleviates Cardiomyopathy Phenotypes Caused by Short-Chain Enoyl-Coa Hydratase 1 Deficiency.JACC. Basic to translational science · 2022Article
- Pathogenic Biallelic Mutations in ECHS1 in a Case with Short-Chain Enoyl-CoA Hydratase (SCEH) Deficiency-Case Report and Literature Review.International journal of environmental research and public health · 2022Review
- Valine metabolites analysis in ECHS1 deficiency.Molecular genetics and metabolism reports · 2021Article
- Exploring triheptanoin as treatment for short chain enoyl CoA hydratase deficiency.Annals of clinical and translational neurology · 2021Article
- Clinical exome sequencing reveals a mutation in PDHA1 in Leigh syndrome: A case of a Chinese boy with lethal neuropathy.Molecular genetics & genomic medicine · 2021Article
- Novel presentations associated with a PDHA1 variant - Alternating hemiplegia in Hemizygote proband and Guillain Barre Syndrome in Heterozygote mother.European journal of paediatric neurology : EJPN : official journal of the European Paediatric Neurology Society · 2021Article
- Differential mitochondrial proteomic analysis of A549 cells infected with avian influenza virus subtypes H5 and H9.Virology journal · 2021Article
- ECHS1 disease in two unrelated families of Samoan descent: Common variant - rare disorder.American journal of medical genetics. Part A · 2021Article
- Article
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Authors and funding
10 authors at 6 institutions in 2 countries.
Funding
Abstract
Mutations in ECHS1 result in short-chain enoyl-CoA hydratase (SCEH) deficiency which mainly affects the catabolism of various amino acids, particularly valine. We describe a case compound heterozygous for ECHS1 mutations c.836T>C (novel) and c.8C>A identified by whole exome sequencing of proband and parents. SCEH deficiency was confirmed with very low SCEH activity in fibroblasts and nearly absent immunoreactivity of SCEH. The patient had a severe neonatal course with elevated blood and cerebrospinal fluid lactate and pyruvate concentrations, high plasma alanine and slightly low plasma cystine. 2-Methyl-2,3-dihydroxybutyric acid was markedly elevated as were metabolites of the three branched-chain α-ketoacids on urine organic acids analysis. These urine metabolites notably decreased when lactic acidosis decreased in blood. Lymphocyte pyruvate dehydrogenase complex (PDC) activity was deficient, but PDC and α-ketoglutarate dehydrogenase complex activities in cultured fibroblasts were normal. Oxidative phosphorylation analysis on intact digitonin-permeabilized fibroblasts was suggestive of slightly reduced PDC activity relative to control range in mitochondria. We reviewed 16 other cases with mutations in ECHS1 where PDC activity was also assayed in order to determine how common and generalized secondary PDC deficiency is associated with primary SCEH deficiency. For reasons that remain unexplained, we find that about half of cases with primary SCEH deficiency also exhibit secondary PDC deficiency. The patient died on day-of-life 39, prior to establishing his diagnosis, highlighting the importance of early and rapid neonatal diagnosis because of possible adverse effects of certain therapeutic interventions, such as administration of ketogenic diet, in this disorder. There is a need for better understanding of the pathogenic mechanisms and phenotypic variability in this relatively recently discovered disorder.
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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.