Editors' Note: Use of Whole-Genome Sequencing for Mitochondrial Disease Diagnosis.

Abstract

Investigators at the Mitochondrial Disease Clinic at Royal North Shore Hospital (Sydney, Australia) prospectively recruited 242 patients who satisfied the Nijmegen criteria for possible, probable, or definite mitochondrial disease (MD). The investigators tested the variant detection rate for a variety of mitochondrial disorders using whole-genome sequencing (WGS) of peripheral blood. Disease-causing variants were found in 53.7% of tested individuals. With more widespread availability and the decreasing cost of WGS, it may become more frequently used as a first-line diagnostic approach in patients with suspected MD. Dr. Schon acknowledged one rare MD, alpha-methylacyl-CoA racemase deficiency, which has been reported in slightly more than a dozen cases to date. Although it may be rare, Dr. Schon maintains that the condition is likely underdiagnosed. The authors agreed and emphasized that dietary restriction of pristanic acid may lessen the risk of severe neurologic disease and manifestations such as seizures and stroke-like episodes. The growing use of technologies such as WGS may facilitate earlier identification and effective treatment of patients with this and other MDs, especially with enriched populations. Investigators at the Mitochondrial Disease Clinic at Royal North Shore Hospital (Sydney, Australia) prospectively recruited 242 patients who satisfied the Nijmegen criteria for possible, probable, or definite mitochondrial disease (MD). The investigators tested the variant detection rate for a variety of mitochondrial disorders using whole-genome sequencing (WGS) of peripheral blood. Disease-causing variants were found in 53.7% of tested individuals. With more widespread availability and the decreasing cost of WGS, it may become more frequently used as a first-line diagnostic approach in patients with suspected MD. Dr. Schon acknowledged one rare MD, alpha-methylacyl-CoA racemase deficiency, which has been reported in slightly more than a dozen cases to date. Although it may be rare, Dr. Schon maintains that the condition is likely underdiagnosed. The authors agreed and emphasized that dietary restriction of pristanic acid may lessen the risk of severe neurologic disease and manifestations such as seizures and stroke-like episodes. The growing use of technologies such as WGS may facilitate earlier identification and effective treatment of patients with this and other MDs, especially with enriched populations.