{
  "abstract": "Short-chain enoyl-CoA hydratase (ECHS1) catalyzes the hydration of C4-C6 acyl-CoA molecules to produce ATP in fatty acid {beta}-oxidation. Deficiency of the ECHS1 enzyme, ECHS1D, is a rare autosomal recessive disorder that presents with a large and pleomorphic clinical spectrum. We present the largest comprehensive study of known diagnosed ECHS1D patients to date, reporting 26 new patients and 8 novel variants in conjunction with a literature review of 87 previously reported patients. All patients were categorized into neonatal, infantile, and late-onset groups based on age of onset and clinical course. Neonatal-onset cases were characterized by early and severe multisystem disease, often with lactic acidosis, hypotonia, cardiomyopathy, and high early mortality (62.5%). The infantile-onset group was heterogeneous, but many exhibited hallmark features such as dystonia, developmental delay, and basal ganglia involvement on neuroimaging. Mortality was significantly lower than the neonatal cohort (24.4%). Late-onset patients had more localized neurologic symptoms, particularly dystonia, and significantly lower mortality overall (0%). Moreover, we report a 37.5% survival rate in newly reported neonatal onset patients compared with 18.2% in prior reports, possibly reflective of earlier recognition of ECHS1D and greater utilization of therapies including N-acetylcysteine, sodium dichloroacetate, and valine-restricted diet.",
  "abstract_shown": true,
  "affiliations": [
    "Icahn School of Medicine"
  ],
  "article_type": "PUBLISHAHEADOFPRINT",
  "arxiv": null,
  "author_total": 35,
  "authors": [
    {
      "name": "C. Kong"
    },
    {
      "name": "C. Alves"
    },
    {
      "name": "G.-F. Vogel"
    },
    {
      "name": "R. Xiao"
    },
    {
      "name": "I. Anselm"
    },
    {
      "name": "G. Berry"
    },
    {
      "name": "J. F. Cabello"
    },
    {
      "name": "V. Cornejo"
    },
    {
      "name": "A. Cortes Fernandez"
    },
    {
      "name": "G. Enns"
    },
    {
      "name": "M. Gomez"
    },
    {
      "name": "C. Haldeman-Englert"
    },
    {
      "name": "S. Hollander"
    },
    {
      "name": "A. M. Innes"
    },
    {
      "name": "E. Jannotta"
    },
    {
      "name": "A. Kochhar"
    },
    {
      "name": "J. Kopesky"
    },
    {
      "name": "A. Larson"
    },
    {
      "name": "C. Lee"
    },
    {
      "name": "M. Lezcano"
    },
    {
      "name": "R. Li"
    },
    {
      "name": "M. Lines"
    },
    {
      "name": "J. Morrison"
    },
    {
      "name": "M. Muriello"
    },
    {
      "name": "E. Null"
    },
    {
      "name": "L. Pena-Quintana"
    },
    {
      "name": "E. Phelps"
    },
    {
      "name": "M. Saifeddine"
    },
    {
      "name": "M. C. Sanabria"
    },
    {
      "name": "R. P. Saneto"
    },
    {
      "name": "E. Shelkowitz"
    },
    {
      "name": "C. Tise"
    },
    {
      "name": "J. L. K. Van Hove"
    },
    {
      "affs": [
        0
      ],
      "name": "I. Elsharkawi"
    },
    {
      "name": "R. D. Ganetzky"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/b9jrgjb1jfk3k.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.11.05.26366953",
  "fulltext_url": "https://www.medrxiv.org/content/10.64898/2026.11.05.26366953v1.full",
  "id": "b9jrgjb1jfk3k",
  "issns": [],
  "landing_url": "https://www.medrxiv.org/content/10.64898/2026.11.05.26366953v1",
  "language": null,
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "medrxiv",
      "genetic and genomic medicine"
    ]
  ],
  "openalex": null,
  "pdf_url": "https://www.medrxiv.org/content/10.64898/2026.11.05.26366953v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-11-05",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/b9jrgjb1jfk3k.ris",
  "sources": [
    {
      "first_seen": "2026-11-06T00:21:02Z",
      "native_id": "10.64898/2026.11.05.26366953",
      "source": "medrxiv",
      "url": "https://www.medrxiv.org/content/10.64898/2026.11.05.26366953v1"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "medrxiv:genetic and genomic medicine",
      "subfield": "human-genetics"
    }
  ],
  "title": "A multi-center retrospective chart analysis identifying clinical, biochemical, and radiographic signatures of short-chain enoyl-CoA hydratase (ECHS1) deficiency",
  "title_text": "A multi-center retrospective chart analysis identifying clinical, biochemical, and radiographic signatures of short-chain enoyl-CoA hydratase (ECHS1) deficiency",
  "type": "preprint",
  "updated_at": "2026-11-07T00:20:51Z",
  "url": "https://research.draconitic.com/paper/b9jrgjb1jfk3k",
  "venue": "medRxiv",
  "versions": []
}