Open AccessDystonia‐ataxia syndrome with permanent torsional nystagmus caused by ECHS1 deficiency
Author(s) -
Ronchi Dario,
Monfrini Edoardo,
Bonato Sara,
Mancinelli Veronica,
Cinnante Claudia,
Salani Sabrina,
Bordoni Andreina,
Ciscato Patrizia,
Fortunato Francesco,
Villa Marianna,
Di Fonzo Alessio,
Corti Stefania,
Bresolin Nereo,
Comi Giacomo P.
Publication year - 2020
Publication title -
annals of clinical and translational neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.824
H-Index - 42
ISSN - 2328-9503
DOI - 10.1002/acn3.51025
Subject(s) - medicine , ataxia , proband , choreoathetosis , exome sequencing , dystonia , endocrinology , nystagmus , phenotype , valine , mutation , genetics , amino acid , audiology , gene , biology , psychiatry
Biallelic mutations in ECHS1 , encoding the mitochondrial enoyl‐CoA hydratase, have been associated with mitochondrial encephalopathies with basal ganglia involvement. Here, we describe a novel clinical presentation consisting of dystonia‐ataxia syndrome with hearing loss and a peculiar torsional nystagmus observed in two adult siblings. The presence of a 0.9‐ppm peak at MR spectroscopy analysis suggested the accumulation of branched‐chain amino acids. Exome sequencing in index probands identified two ECHS1 mutations, one of which was novel (p.V82L). ECHS1 protein levels and residual activities were reduced in patients’ fibroblasts. This paper expands the phenotypic spectrum observed in patients with impaired valine catabolism.