Leber's hereditary optic neuropathy like disease in MT-ATP6 variant m.8969G>A

Abstract

Purpose: To describe a case with Leber's hereditary optic neuropathy (LHON) like optic atrophy in the presence of MT-ATP6 gene variant m.8969G > A.

Observations: A 20-year-old patient with a history of mild developmental delay, mild cognitive impairment, and positional tremor presented with subacute painless visual loss over a few weeks. Mitochondrial genome sequencing revealed a variant in MT-ATP6, m.8969G > A (p.Ser148Asn). This variant was previously reported in association with mitochondrial myopathy, lactic acidosis, and sideroblastic anemia (MLASA) and with nephropathy, followed by brain atrophy, muscle weakness and arrhythmias, but not with optic atrophy.

Conclusions and importance: Rare variants in MT-ATP6 can also cause LHON like optic atrophy. It is important to perform further genetic analysis of mitochondrial DNA in genetically unsolved cases suspected of Leber's hereditary optic neuropathy to confirm the clinical diagnosis.

Keywords: Leber's hereditary optic neuropathy; MT-ATP6; Optic atrophy.

Fig. 1

Fundoscopy and optical coherence tomography (OCT) imaging of the optic nerve. Pale optic discs were seen on fundoscopy and retinal nerve fiber layer was attenuated bilaterally on the OCT.

Fig. 2

Optical coherence tomography scan of the macula from the last follow up (30y). On the right eye, retinal nerve fiber layer is markedly attenuated. On the left eye, there are few intraretinal fluid collections.

Fig. 3

A. Family tree, showing the segregation analysis and heteroplasmic state (%) in blood of different family members. Sister, mother and the maternal grandmother of the patient had the same variant with a heteroplasmic state of 33 %, 15 % and 22 %, respectively. B. Results of mitochondrial respiration rate analysis via seahorse respirometer among cell clones with different heteroplasmy levels showing decreased oxygen consumption levels in homoplasmic clones compared to the heteroplasmic clone and two healthy controls. C. Levels of complex V in cell clones with different heteroplasmy levels. Complex V levels varied and were not consistently low in homoplasmic clones.