The m.14453G > A mutation in MT-ND6 has been described in a few patients with mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes or Leigh syndrome. However, the clinical spectrum and molecular characteristics are unclear. Here, we present four infantile-onset patients with m.14453G > A-associated Leigh syndrome. All four patients had brainstem lesions with basal ganglia lesions, and two patients had cardiac manifestations. Decreased ND6 protein expression and immunoreactivity were observed in patient-derived samples. There was no clear correlation between heteroplasmy levels and onset age or between heteroplasmy levels and phenotype; however, infantile onset was associated with Leigh syndrome. [ABSTRACT FROM AUTHOR]