Genotype and phenotype characteristics of Leber hereditary optic neuropathy (LHON) patients in Slovenia

Abstract

Purpose : To study genotype and phenotype characteristics of Leber Hereditary Optic Neuropathy patients in population of Slovenia.

Methods : All patients with suspected LHON were referred to Eye Clinic, University Medical Center Ljubljana, the only tertiary centre for neuro-ophthalmology in Slovenia with population of 2 million. Inclusion criteria were bilateral optic neuropathy with no other confirmed causes of optic neuropathy. In all, three typical mutations (m.3460G>A, m.11778G>A, m.14484T>C) were screened first. If negative, complete mtDNA sequencing (NGS) was carried out whenever possible. All patients had bilateral loss of visual acuity (VA), colour vision and central visual field, and were assessed by Snellen and Ishihara tables, Octopus visual fields, SD-OCT, and by electrophysiology.

Results : Thirty seven patients met inclusion criteria, 32 were of Slovenian, 3 Croatian, 1 Serbian and 1 Albanian ethnicity. Out of these 37 patients, 5 (13.51 %) were positive for one of the 3 typical mutations (2 of Slovenian ethnicity). Out of 32 that were negative, 15 underwent NGS, among which 11 (29.7% of 37) were positive for atypical mutations. NGS for the rest of the patients is ongoing. Based on this data, current prevalence of LHON in Slovenia is 17 in 2 million (appx. 1:120.000). Electrophysiology showed reduced PERG N95 wave (in appx. 50 % already in hyperaemic stage), VEP showed delayed and reduced P100 wave. Two Slovenian patients with atypical mutations (LHON 1 and 3, Table1) and 1 patient with typical mutation of Albanian ethnicity (LHON 13, Table1) showed significant improvement of VA (Table 2) and visual field. Latency of the P100 wave improved but amplitudes remained low, whilst PERG N95 wave amplitudes did not improve. OCT showed thinning of ganglion cell and nerve fiber layers, which remained unchanged on follow up.

Conclusions : Prevalence of LHON amongst Slovenian population is lower in comparison to other countries whilst atypical mutations in Slovenian ethnicity are prevailing (11 of 13, 83%). Two LHON patients, both with the same atypical mutations (A3902G, p.D199G, A15326G, p.T194A), and one with typical mutation (m14484 T>C) have shown significant spontaneous improvement. Based on normalisation of latency of the P100 wave, re-myelination may play a role in visual improvement.

This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.

 

Table 1. Genotype of Slovenian LHON patients

 

Table 2. Course of visual acuity in three patients that improved