Author Response: Use of Whole-Genome Sequencing for Mitochondrial Disease Diagnosis.

Abstract

We strongly agree with Dr. Schon and Prof. Chinnery that alpha-methylacyl-CoA racemase (AMACR) deficiency should be considered in the differential diagnosis of patients presenting with combinations of stroke-like episodes, seizures, encephalopathy, and retinal pigmentary changes.1 As described in our study,1 causative AMACR variants in patients with clinical features suggestive of mitochondrial disease highlight a broader issue of mitochondrial disease phenocopies that require consideration by a comprehensive sequencing approach for suspected mitochondrial disease cases. Examples of this include 3 individuals from 2 families in our study,1 3 individuals in the 100,000 Genomes Project,2 an individual in the study by Theunissen et al,3 and a recent case of an individual with late-onset disease associated with stroke-like episodes and seizures.4