Mitochondrial DNA mutation 14487T>C manifesting as Leber's hereditary optic neuropathy

Dear Sirs Leber’s hereditary optic neuropathy (LHON; OMIM 535000) is a rare maternally inherited disease characterized by subacute bilateral painless loss of central vision caused by mutations in the mitochondrial genome [1]. It predominantly affects young men with an estimated prevalence of 1/30,000–1/45,000 in Europe [2, 3]. The majority of patients (more than 95 %) have one of three mitochondrial DNA point mutations (m.3460G[A, m.11778G[A, m.14484T[C), which all involve genes encoding subunits of NADH-dehydrogenase [4]. Therapeutic approaches aim to interact with the mitochondrial electron transport chain and subgroups of LHON patients might benefit from treatment with idebenone, a potent antioxidant [5]. While visual loss is the primary and generally the most important clinical manifestation in most patients with LHON, other additional neurologic manifestations in much more severe cases have been reported and are called ‘‘LHON plus’’ syndromes, e.g. LHON plus dystonia (LDYT; OMIM 500001). The male patient complained about blurred vision in both eyes for the first time at the age of 16 years. After a few weeks of slowly deteriorating vision, the patient was seen by an ophthalmologist and admitted to hospital for further diagnostic testing with the suspected diagnosis of bilateral optic neuritis. There were no relevant diseases in his past medical or family history. The patient consumes alcohol occasionally, nicotine or any other drugs were denied. MRI of the brain showed a non-specific small, round alteration of signal in the left periventricular white matter which was only detectable on T2. MRI of the spinal cord, standard laboratory tests and cerebrospinal fluid were normal. The patient was treated with a cortisone pulse for 3 days without any improvement and referred to our hospital, 9 weeks after the initial presentation. Visual acuity was 0.6 logMAR OD and 0.9 logMAR OS. Kinetic perimetry revealed bilateral central scotomata Funduscopy and optical coherence tomography (OCT) showed mild disc swelling with temporal pallor and atrophy OS (Fig. 1). VEPs showed inconsistent latencies and pathologic very low amplitudes. Aside from the impaired vision the patient did not complain about any other symptoms and detailed neurological was normal. Repeated brain MRI with spectroscopy confirmed the non-specific white matter lesion and showed a discrete signal accentuation of the left optic nerve. Spectroscopy was normal with no abnormal lactate peak. Electrocardiogram, & M. Eckenweiler matthias.eckenweiler@uniklinik-freiburg.de