RESUMO
Objective: The gene MT-TF encodes the mitochondrial tRNA of phenylalanine (tRNAphe). Its variations have been described as extremely rare etiologies of a variety of mitochondrial phenotypes. Methods: By means of whole-exome sequencing (WES), we detected a novel likely causative MT-TF variant (m.610T>C) in a family presenting with a combined movement disorder and epilepsy phenotype. The variant was present at 97% heteroplasmy in the peripheral blood and in a homoplasmic state in skin fibroblast-derived DNA. Results: The inaugural manifestation in the index patient was new-onset refractory myoclonic status epilepticus (NORSE) at the age of 29 years. Her son presented later with developmental regression and myoclonic epilepsy. On the beginning of valproate because of ongoing myoclonic seizures, the index patient developed a generalized brain edema requiring bilateral craniotomy. In the course of the disease, epileptic manifestations abated, and both patients developed a severe movement disorder phenotype with prominent spastic-dystonic features. Both patients did not display any further sign of mitochondrial disease. Discussion: Our report expands the clinicogenetic background of tRNAphe disease spectrum and highlights pitfalls in the diagnostics and management of mitochondrial epilepsy. The present findings advocate the introduction of rapid genetic testing in the diagnostic flow chart of NORSE in adults.