Phenotypic spectrum of short-chain enoyl-Coa hydratase-1 (ECHS1) deficiency

Masnada, Silvia; Parazzini, Cecilia; Bini, P; Barbarini, Mario; Alberti, Luisella; Valente, Marialuisa; Chiapparini, Luisa; Silvestri, Annalisa De; Doneda, Chiara; Iascone, Maria; Saielli, Laura Assunta; Cereda, Cristina; Veggiotti, Pierangelo; Corbetta, Carlo; Tonduti, Davide

doi:10.1016/j.ejpn.2020.07.007

Cited by 20 publications

(26 citation statements)

References 24 publications

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“…We did not find another reported case with similarly combined alleles as our case. All cases are described in Table 3 [ 4 , 27 , 28 , 29 , 30 , 31 , 32 ].…”

Section: Discussionmentioning

confidence: 99%

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

Muntean

Tripon

Bogliș

et al. 2022

IJERPH

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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.

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“…We did not find another reported case with similarly combined alleles as our case. All cases are described in Table 3 [ 4 , 27 , 28 , 29 , 30 , 31 , 32 ].…”

Section: Discussionmentioning

confidence: 99%

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

Muntean

Tripon

Bogliș

et al. 2022

IJERPH

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“…5 Masnada et al distinguished four phenotypes of ECHS1 deficiency: (1) a severe neonatal form with fatal course, (2) a severe infantile form with slower neurological deterioration, (3) a slowly progressive infantile form, and (4) a form with paroxysmal exercise-induced dystonic attacks. 4,5 We classified a severe infantile case with slower neurological deterioration with typical symptoms.…”

Section: Discussionmentioning

confidence: 99%

“…If ECHS1 loses its function, the highly reactive intermediates accumulate and cause an impairment of adenosine triphosphate (ATP) production, metabolic acidosis, and subsequently a brain damage. [4][5][6] Here, we report data gathered on a patient presenting with the homozygous mutation c.476A > G in ECHS1 gene with severe encephalopathy and developmental delay.…”

Section: Introductionmentioning

confidence: 99%

A Case of ECHS1 Deficiency with Severe Encephalopathy and Status Epilepticus after a Propofol Sedation: Case Report

2022

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Background Short-chain enoyl-CoA hydratase (ECHS1) deficiency is a rare metabolic disorder. Concerned patients present with Leigh syndrome symptoms or a Leigh-like syndrome. Only 58 patients are known worldwide. The ECHS1 is a key component in β-oxidation and valine catabolic pathways. Case Here we report a 6-month-old Lebanese boy born to consanguineous parents. He presented an increased muscle tone, hyperexcitability, feeding problems, horizontal nystagmus, and developmental delay. Magnetic resonance imaging of the brain revealed frontal brain atrophy, corpus callosum atrophy, and T2 hyperintensity in pallidum, internal capsule, pons, and thalamus. In the postsedation phase, the patient displayed a sudden generalized seizure with transition to status epilepticus. Therefore, we conducted metabolic examinations, which showed elevated levels of 2-methyl-2,3-DiOH-butyrate and 3-methylglutaconate in urine. Single exome sequencing revealed the homozygous mutation c.476A > G in the ECHS1 gene. Conclusion This case report describes the clinical symptoms and the diagnostics of ECHS1 deficiency. It shows the importance of further metabolic and genetic testing of patients with motoric conspicuities and developmental delay. It is important to be cautious with propofol sedation of patients who present an unknown neurological disorder, when metabolic disturbance or especially mitochondriopathy is suspected.

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“…1 ) [1] , [2] , [3] , [4] . ECHS1 deficiency (OMIM 602292 ) causes Leigh syndrome and/or exercise-induced dystonia in milder forms and more than 60 cases have been reported [5] , [6] , [7] . Patients with ECHS1 deficiency typically present with developmental delay and neurological deterioration from the neonatal or early infantile period, presenting features of Leigh syndrome with basal ganglia lesions and lactic acidemia [8 , 9 , 10 , 11] .…”

Section: Introductionmentioning

confidence: 99%

Valine metabolites analysis in ECHS1 deficiency

Kuwajima

Kojima

Osaka

et al. 2021

Molecular Genetics and Metabolism Reports

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Short-chain enoyl-CoA hydratase (ECHS1) is involved in amino acid and fatty acid catabolism in mitochondria and its deficiency causes Leigh syndrome or exercise-induced dystonia. More than 60 patients with this condition have been reported till date. The accumulation of intermediate metabolites of valine is assumed to be responsible for the cytotoxicity. Since protein restriction, including valine reportedly improves neurological symptoms, it is essential to consider the possible incidence of and diagnose ECHS1 syndrome in the earlier stages. This study reported the liquid chromatography with tandem mass spectrometry (LC-MS/MS) urine and plasma metabolite analysis in six cases, including four new cases with ECHS1 deficiency. The values of urine cysteine/cysteamine conjugates from valine metabolites, S-(2-carboxypropyl) cysteine/cysteamine from methacrylyl-CoA, and S-(2-carboxyethyl) cysteine/cysteamine from acryloyl-CoA were separated between six patients and six normal controls. The LC-MS/MS analysis revealed that these metabolites can be used for the early diagnosis and evaluation of diet therapy.

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Phenotypic spectrum of short-chain enoyl-Coa hydratase-1 (ECHS1) deficiency

Cited by 20 publications

References 24 publications

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

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

A Case of ECHS1 Deficiency with Severe Encephalopathy and Status Epilepticus after a Propofol Sedation: Case Report

Valine metabolites analysis in ECHS1 deficiency

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