Expedited Exome Re-analysis following Deep Phenotyping and Muscle Biopsy in Suspected Mitochondrial Disorder

Abstract

BackgroundExome sequencing (ES) is a useful tool in diagnosing suspected mitochondrial disease but can miss pathogenic variants for several reasons. Additional testing, such as muscle biopsy or biochemical testing, can be helpful in exome-negative cases. CaseWe report a patient who presented with repeated episodes of lactic acidosis and failure to thrive. ES and mitochondrial sequencing was initially negative but given clinical suspicion for mitochondrial disease was still high. After muscle biopsy showed evidence of mitochondrial dysfunction, the ES was re-analyzed and revealed novel variants in AARS2. ConclusionThis case demonstrates the importance of muscle biopsy and biochemical testing in evaluating patients with a high suspicion of mitochondrial disease, even in the genomics era. Closed-loop communication between molecular genetics laboratories and clinical geneticists an important step to help establish diagnosis in unsolved cases.