Dystonia-ataxia syndrome with permanent torsional nystagmus caused by ECHS1 deficiency.
Dario RonchiEdoardo MonfriniSara BonatoVeronica MancinelliClaudia CinnanteSabrina SalaniAndreina BordoniPatrizia CiscatoFrancesco FortunatoMarianna VillaAlessio di FonzoStefania CortiNereo BresolinGiacomo Pietro ComiPublished in: Annals of clinical and translational neurology (2020)
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.
Keyphrases
- early onset
- end stage renal disease
- amino acid
- oxidative stress
- deep brain stimulation
- chronic kidney disease
- ejection fraction
- intellectual disability
- hearing loss
- newly diagnosed
- case report
- peritoneal dialysis
- high resolution
- magnetic resonance
- magnetic resonance imaging
- prognostic factors
- copy number
- fatty acid
- computed tomography
- small molecule
- binding protein
- protein protein
- smoking cessation
- childhood cancer