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Review
. 2022 Feb 13;19(4):2088.
doi: 10.3390/ijerph19042088.

Pathogenic Biallelic Mutations in ECHS1 in a Case with Short-Chain Enoyl-CoA Hydratase (SCEH) Deficiency-Case Report and Literature Review

Carmen Muntean  1   2 , Florin Tripon  3   4 , Alina Bogliș  3   4 , Claudia Bănescu  3   4
Affiliations
Review

Pathogenic Biallelic Mutations in ECHS1 in a Case with Short-Chain Enoyl-CoA Hydratase (SCEH) Deficiency-Case Report and Literature Review

Carmen Muntean et al. Int J Environ Res Public Health. .

Abstract

ECHS1 gene mutations are known to cause mitochondrial short-chain enoyl-CoA hydratase 1 deficiency, a neurodegenerative disorder characterized by psychomotor development delay, lactic acidosis, and basal ganglia lesions resembling Leigh syndrome. Short-chain enoyl-CoA hydratase 1 (ECHS1) deficiency is a very rare and new disorder, with a wide phenotypic spectrum and different outcomes ranging from neonatal death to survival into adulthood. Since the identification of ECHS1 deficiency in 2014, almost 63 patients with pathogenic mutations in the ECHS1 gene have been described to date. This paper focuses on the clinical and molecular findings as well as the evolution of a Caucasian girl diagnosed with ECHS1 deficiency who carries a new compound heterozygous mutation in the ECHS1 gene. Polymorphic symptoms, namely failure to thrive, significant global developmental delay/regression, movement disorders, ocular abnormalities, hearing loss, seizure, and cardiac myopathy, may be a challenge in mitochondrial disorder suspicion. Early diagnosis, an appropriate diet with valine restriction, and trigger avoidance are essential, as there is no effective therapy for the disease. This disorder influences life quality in these patients and their caregivers, and it has the potential to be fatal.

Keywords: ECHS1 gene; Leigh syndrome; diet; genotype-phenotype correlations; neurodevelopment disorder; valine.

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Conflict of interest statement

The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results. This paper has not been published previously and is not under consideration for publication elsewhere. Publication of this work is approved by all authors.

Figures

Figure 1
Figure 1
Coronal T2 TIRM dark fluid MRI sequences revealing bilateral basal ganglia hyperintensities and cerebral atrophy.
Figure 2
Figure 2
The pedigree and electropherogram illustrate the compound heterozygous mutation in the ECHS1 gene in the affected child.
Figure 3
Figure 3
Structure of human enoyl-coenzyme A (CoA) hydratase short chain 1, encoded by ECHS1 gene. (A) the crystal structure at a resolution of 2.55 Å, from the PDB protein databank, structure 2HW5 [18]. (B) Missense mutations affect the homohexameric ECHS1 structure. (the location of the changes are represented with green in 2HW5, and were visualized by using Mol * Viewer, a modern web app for 3D visualization and analysis) [19].
Figure 4
Figure 4
Patient weight-for-length chart, from birth to present. The growth curve reveals a significant weight gain after PEG (percutaneous endoscopic gastrostomy) tube placement and a valine-restricted diet. (chart realized with WHO Anthro v3.2.2 software).
See this image and copyright information in PMC

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