iarjmcrIARJMCRIARJMCR2709-3220https://doi.org/10.47310/iarjmcr.2021.v02i02.008The m.13513 G>A Variant Is Pathogenic and Phenotypically HeterogeneousJosefFinstererKlinik Landstrasse, Messerli Institute, Vienna, AustriaThe recent report by Liang et al. describes a 15-month-old male presenting with Leigh syndrome associated with the mitochondrial DNA variant m.13513G>A. While the case is clinically relevant, several limitations restrict the strength of the conclusions. Review of the literature shows that this variant has been reported in at least 33 individuals, exhibiting a wide phenotypic spectrum ranging from Leigh syndrome and Leigh-like presentations to MELAS, LHON, PEO, and non-syndromic manifestations such as optic atrophy, myopathy, cardiomyopathy, seizures, or ataxia. Reported heteroplasmy rates vary markedly across tissues (0–86%), underscoring the need for comprehensive multisystem evaluation. In the index patient, essential clinical information is missing, particularly regarding the cause of respiratory failure, cardiac evaluations, long-term rhythm monitoring, and therapeutic interventions for Wolff-Parkinson-White syndrome. Additionally, the extent of multisystem involvement was insufficiently explored despite the multisystemic nature of mitochondrial disorders. No biochemical analyses or muscle investigations were performed to assess respiratory chain function, which is particularly relevant given the expected complex I deficiency associated with ND5 mutations. The authors’ recommendation to specifically screen Chinese patients with Leigh syndrome and WPW for the m.13513G>A variant appears too narrow; instead, full mitochondrial DNA sequencing followed by exome analysis, when necessary, represents a more appropriate diagnostic approach due to the considerable genetic and phenotypic heterogeneity of Leigh syndrome. Addressing these gaps would strengthen the conclusions and clinical relevance of the report.