Introduction: The majority of Caucasian patients with Leber Hereditary Optic Neuropathy (LHON) harbor one of three primary pathogenic mitochondrial DNA (mtDNA) variants, which are usually present in homoplasmy in leukocytes. Most of the remaining cases have been linked to rare heteroplasmic pathogenic variants, that typically require a mutational load of more than 60% to result in phenotypic expression. Case Presentation: An 18-year-old Caucasian man presented with sudden visual loss in the left eye. Eye examination revealed hyperemic optic discs with retinal vascular tortuosity and subtle peripapillary telangiectasia, reminiscent of LHON, but initial mtDNA analysis was negative. Best-corrected visual acuity (BCVA) continued to decrease despite systemic corticotherapy and subsequent treatment with plasma exchange. The patient then experienced visual loss in the fellow eye, with BCVA in both eyes deteriorating to ‘counting fingers’. Subsequent screening of complete mtDNA by massive parallel sequencing of leukocyte DNA identified a variant NC₀12920. 1 (MT-ND5): m. 13042G>A, p. (Ala236Thr), in heteroplasmy, with a variant load of around 23. 8%. Progressive visual recovery was observed in both eyes, resulting in BCVA of 20/29 in both eyes after four years of follow-up. Conclusion: In patients with a strong clinical suspicion of LHON, complete mitochondrial genome sequencing should be considered when initial testing, typically limited to the three primary mutations, is negative. Furthermore, the diagnosis of LHON should not be dismissed if ‘low’ blood mutant loads are found, as important discrepancies of heteroplasmy levels between different tissues have been reported for variants located in the mitochondrial ND5 gene.
Buelens et al. (Mon,) studied this question.