A multi-center retrospective chart analysis identifying clinical, biochemical, and radiographic signatures of short-chain enoyl-CoA hydratase (ECHS1) deficiency
- 1Icahn School of Medicine
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.
Related
- Identifying Iron Deficiency and Opportunities for IV Iron Supplementation in Patients with Heart Failure with Reduced Ejection Fraction: A Retrospective Cohort Study
- Durable biochemical and radiographic response during toripalimab treatment in MSI-high/TMB-high mCRPC: a case report
- Citrin Deficiency: Biochemical Mechanisms Underlying a Complex Hepatic Metabolic Disorder
- Static vs Expandable Cages in Single-Level Prone Transpsoas Lateral Lumbar Interbody Fusion: A Retrospective Radiographic Cohort Study
- Agreement and Systematic Differences Between Intraoperative ROSA Hip-Knee-Ankle Measurements and Standing Radiographic Alignment After Robotic-Assisted Total Knee Arthroplasty: A Retrospective Agreement Study
BibTeX
@misc{kong2026multicenter,
title = {{A multi-center retrospective chart analysis identifying clinical, biochemical, and radiographic signatures of short-chain enoyl-CoA hydratase (ECHS1) deficiency}},
author = {C. Kong and C. Alves and G.-F. Vogel and R. Xiao and I. Anselm and G. Berry and J. F. Cabello and V. Cornejo and A. Cortes Fernandez and G. Enns and M. Gomez and C. Haldeman-Englert and S. Hollander and A. M. Innes and E. Jannotta and A. Kochhar and J. Kopesky and A. Larson and C. Lee and M. Lezcano and R. Li and M. Lines and J. Morrison and M. Muriello and E. Null and L. Pena-Quintana and E. Phelps and M. Saifeddine and M. C. Sanabria and R. P. Saneto and E. Shelkowitz and C. Tise and J. L. K. Van Hove and I. Elsharkawi and R. D. Ganetzky},
howpublished = {medRxiv},
year = {2026},
month = nov,
doi = {10.64898/2026.11.05.26366953},
url = {https://www.medrxiv.org/content/10.64898/2026.11.05.26366953v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - A multi-center retrospective chart analysis identifying clinical, biochemical, and radiographic signatures of short-chain enoyl-CoA hydratase (ECHS1) deficiency
AU - C. Kong
AU - C. Alves
AU - G.-F. Vogel
AU - R. Xiao
AU - I. Anselm
AU - G. Berry
AU - J. F. Cabello
AU - V. Cornejo
AU - A. Cortes Fernandez
AU - G. Enns
AU - M. Gomez
AU - C. Haldeman-Englert
AU - S. Hollander
AU - A. M. Innes
AU - E. Jannotta
AU - A. Kochhar
AU - J. Kopesky
AU - A. Larson
AU - C. Lee
AU - M. Lezcano
AU - R. Li
AU - M. Lines
AU - J. Morrison
AU - M. Muriello
AU - E. Null
AU - L. Pena-Quintana
AU - E. Phelps
AU - M. Saifeddine
AU - M. C. Sanabria
AU - R. P. Saneto
AU - E. Shelkowitz
AU - C. Tise
AU - J. L. K. Van Hove
AU - I. Elsharkawi
AU - R. D. Ganetzky
PY - 2026
DA - 2026/11/05
PB - medRxiv
DO - 10.64898/2026.11.05.26366953
UR - https://www.medrxiv.org/content/10.64898/2026.11.05.26366953v1
AB - 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.
ER -