Dystonia‐ataxia syndrome with permanent torsional nystagmus caused by ECHS1 deficiency

Ronchi, Dario; Monfrini, Edoardo; Bonato, Sara; Mancinelli, Veronica; Cinnante, Claudia; Salani, Sabrina; Bordoni, Andreina; Ciscato, Patrizia; Fortunato, Francesco; Villa, Marianna; Fonzo, Alessio Di; Corti, Stefania; Bresolin, Nereo; Comi, Giacomo Pietro

doi:10.1002/acn3.51025

Cited by 10 publications

(15 citation statements)

References 20 publications

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“…Quality of life in these patients and their caregivers are influenced by progressive evolution. Prognosis is poor, with a short survival rate of about 70 months, but cases with neonatal deaths or adulthood survival up to 32 years have also been reported [ 41 , 42 ].…”

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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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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“…Biallelic mutations have been found in the ECHS1 gene encoding the enoyl-CoA hydratase protein, and they have been associated with early onset of a Leigh-like syndrome that is characterized by the development of progressive encephalopathy and mitochondrial deficits leading to the development of optic atrophy, developmental delay, and symptoms not related to neuromuscular disorders, such as epilepsy and bilateral hearing loss [ 226 , 227 , 228 ]. Recently, ECHS1 enzyme deficiency has been associated with the development of a new symptomatology associated with dystonia-ataxia syndrome with permanent torsional nystagmus [ 214 ].…”

Section: Alterations Of Mitochondrial Enzymes Impair Neuromuscular Functionsmentioning

confidence: 99%

An Overview of Mitochondrial Protein Defects in Neuromuscular Diseases

et al. 2021

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Neuromuscular diseases (NMDs) are dysfunctions that involve skeletal muscle and cause incorrect communication between the nerves and muscles. The specific causes of NMDs are not well known, but most of them are caused by genetic mutations. NMDs are generally progressive and entail muscle weakness and fatigue. Muscular impairments can differ in onset, severity, prognosis, and phenotype. A multitude of possible injury sites can make diagnosis of NMDs difficult. Mitochondria are crucial for cellular homeostasis and are involved in various metabolic pathways; for this reason, their dysfunction can lead to the development of different pathologies, including NMDs. Most NMDs due to mitochondrial dysfunction have been associated with mutations of genes involved in mitochondrial biogenesis and metabolism. This review is focused on some mitochondrial routes such as the TCA cycle, OXPHOS, and β-oxidation, recently found to be altered in NMDs. Particular attention is given to the alterations found in some genes encoding mitochondrial carriers, proteins of the inner mitochondrial membrane able to exchange metabolites between mitochondria and the cytosol. Briefly, we discuss possible strategies used to diagnose NMDs and therapies able to promote patient outcome.

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“…In contrast, intermediate and mild cases usually have normal laboratory values. A review of the literature 1‐4,6‐29 revealed 67 patients with most suffering the early onset presentation. Average age at death was 28.0 + 43.8 months (range 16 h to 156 months) for 27 early onset patients (age <12 months) for whom age at death was reported.…”

Section: Introductionmentioning

confidence: 99%

“…Short Chain Enoyl Co-A Hydratase (SCEH) deficiency is a phenotypically heterogeneous disorder ranging from an early onset severe progressive Leigh-Like Syndrome with early demise 1,2 to later onset childhood movement disorders. 3,4 Early onset symptoms include hypotonia, respiratory insufficiency, global developmental delay, encephalopathy, sensorineural hearing loss, cardiomyopathy, and bilateral basal ganglia lesions. 5 Less common are the later onset mildly symptomatic patients with varied movement disorders and basal ganglia lesions.…”

Section: Introductionmentioning

confidence: 99%

Exploring triheptanoin as treatment for short chain enoyl CoA hydratase deficiency

Engelstad

Salazar

Koenigsberger

et al. 2021

Ann Clin Transl Neurol

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We explored the benefits of triheptanoin as a treatment for Short Chain Enoyl Co‐A Hydratase (SCEH) deficiency. One child with early onset, severe SCEH Deficiency was treated with triheptanoin, an odd chain oil with anapleurotic properties, for 37 months. Blood and urine chemistry safety measures, motor skills assessment, physical exam, and neurological assessment were monitored over a 27 month period. Modest sustained gains in motor skills, attention, muscle bulk, and strength were observed without any significant adverse effects. Triheptanoin appears to be a promising effective treatment for SCEH Deficiency.

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Dystonia‐ataxia syndrome with permanent torsional nystagmus caused by ECHS1 deficiency

Cited by 10 publications

References 20 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

An Overview of Mitochondrial Protein Defects in Neuromuscular Diseases

Exploring triheptanoin as treatment for short chain enoyl CoA hydratase deficiency

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