Paroxysmal and non-paroxysmal dystonia in 3 patients with biallelic ECHS1 variants: Expanding the neurological spectrum and therapeutic approaches.

DOI
Publisher DOI
PubMed ID
32858208
Abstract
BACKGROUND

ECHS1 encodes the mitochondrial short chain enoyl CoA hydratase 1 (SCEH). Biallelic ECHS1 variants have been associated with Leigh-like presentations and milder phenotypes with paroxysmal exercise-induced dystonia.

PATIENTS/METHODS

We used exome sequencing to investigate molecular bases of paroxysmal and non-paroxysmal dystonia in three patients and performed functional studies in fibroblasts. Disease presentation and response upon dietary interventions were documented.

RESULTS

We identified compound heterozygous ECHS1 missense variants in all individuals; all of them harbouring an c.518C > T (p.Ala173Val) variant. SCEH activity was impaired in patients' fibroblasts, respiratory chain-, and pyruvate-dehydrogenase-complex activities were normal in one individual. Patient 1 presented from the age of 2.5 years on with paroxysmal opisthotonic posturing. Patient 2 had a first metabolic crisis at the age 20 months developing recurrent exercise-induced dystonic episodes. Disease history of patient 3 was unremarkable for neurological findings until he first presented at the age of 20 years with persistent dystonia. Ketogenic diet had beneficial effects in patient 1. Neither ketogenic nor low protein diets led to milder symptoms in patient 2. Patient 3 benefits from low protein diet with improvement of his torticollis.

CONCLUSIONS

In line with literature, our findings corroborate that the pathogenic ECHS1 variant c.518C > T (p.Ala173Val) is associated with milder phenotypes characterized by paroxysmal and non-paroxysmal dystonia. Because of the potentially treatable defect, especially in milder affected patients, it is important to consider SCEH deficiency not only in patients with Leigh-like syndrome but also in patients with paroxysmal dystonia and normal neurological findings between episodes.
Date Issued
2020-11
Publication Type
Article
Subject(s)
Subjects
Dystonia ECHS1 Exercise-induced Ketogenic diet Opisthotonus Paroxysmal
Language(s)
en
Author(s)
Illsinger, Sabine
Korenke, G Christoph
Boesch, Sylvia
Nocker, Michael
Karall, Daniela
Laugwitz, Lucia
Mayr, Johannes A
Scholl-Bürgi, Sabine
Freisinger, Peter
Kowald, Tobias
Kölker, Stefan
Prokisch, Holger
Haack, Tobias B
Additional Credits
Journal
European journal of medical genetics
Publisher
Elsevier
ISSN
1878-0849
Access(Rights)
restricted
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