title: ECHS1 deficiency-associated paroxysmal exercise-induced dyskinesias: case presentation and initial benefit of intervention.
abstract: Paroxysmal exercise-induced dyskinesias (PED) are paroxysmal dyskinesias which manifest as dystonic movements brought on by sustained exercise. ECHS1 deficiency-induced EID was recently described by Olgiati et al. Our patient is an 8-year-old boy, who presented with intermittent episodes of stiffness and contractions affecting the legs which were always brought on by vigorous exertion. They began with curling of the toes and flexion, followed by stiffening of gait. These episodes were asymmetric, uncomfortable and often began in the left leg, often spreading to the right leg. They generally lasted for about 30-40 min. The phenomenology was noted to be dystonic affecting mostly the left leg, with equinus at the ankle and hyperextension at the knee. MRI of the brain showed regions of increased T2 and FLAIR signal and of T1 low signal in the globus pallidus bilaterally with mild diffusion restriction. Using Ambry's ExomeNextTM, an integrated exome sequencing assay, the patient was found to be heterozygous for alterations in the ECHS1 gene: missense mutations in c.518C>T (p.A173V) and c.817A>G (p.K273E). After 3 months of treatment with a mitochondrial cocktail, the patient reported that his attacks were somewhat less frequent and less severe. We decided to continue the patient on the cocktail and prescribed clonazepam 0.5 mg 1 tab to be given, as needed, for acute dystonic episodes of severe degree. The missense mutation c.817A>G has never been associated with PED before. Further, we present the first case of ECH1-associated PED with initial symptomatic improvement with a mitochondrial cocktail.
authors.affiliation: Department of Neurology, Henry Ford Hospital, 2799 W. Grand Boulevard, K-11, Detroit, MI, 48202, USA. amahaja1@hfhs.org.
authors.forename: Abhimanyu
authors.identifier: http://orcid.org/0000-0001-8807-6672
authors.initials: A
authors.lastname: Mahajan
authors.affiliation: Department of Neurology, Henry Ford Hospital, 2799 W. Grand Boulevard, K-11, Detroit, MI, 48202, USA.
authors.forename: Jules
authors.initials: J
authors.lastname: Constantinou
authors.affiliation: Department of Neurology, Henry Ford Hospital, 2799 W. Grand Boulevard, K-11, Detroit, MI, 48202, USA.|Department of Neurology and Ophthalmology, Michigan State University, East Lansing, MI, USA.
authors.forename: Christos
authors.initials: C
authors.lastname: Sidiropoulos
mesh_terms: D001921:Brain / Q000000981:diagnostic imaging; D002648:Child; D002819:Chorea / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics*; D003937:Diagnosis, Differential; D004746:Enoyl-CoA Hydratase / Q000172:deficiency* / Q000235:genetics*; D006801:Humans; D008297:Male; D020125:Mutation, Missense; D016896:Treatment Outcome
chemical_list: C000600529:ECHS1 protein, human; D004746:Enoyl-CoA Hydratase
keywords: Exercise-induced dystonia; Genetic dystonia; Movement disorders; Paroxysmal dystonia