A Typical Case Presentation with Spontaneous Visual Recovery in Patient Diagnosed with Leber Hereditary Optic Neuropathy Due to Rare Point Mutation in MT-ND4 Gene (m.11253T>C) and Literature Review

Abstract

Leber hereditary optic neuropathy (LHON) is one of the most common inherited mitochondrial optic neuropathies, caused by mitochondrial DNA (mtDNA) mutations. Three most common mutations, namely m.11778G>A, m.14484T>G and m.3460G>A, account for the majority of LHON cases. These mutations lead to mitochondrial respiratory chain complex I damage. Typically, LHON presents at the 15–35 years of age with male predominance. LHON is associated with severe, subacute, painless bilateral vision loss and account for one of the most common causes of legal blindness in young individuals. Spontaneous visual acuity recovery is rare and has been reported in patients harbouring m.14484T>C mutation. Up to date LHON treatment is limited. Idebenone has been approved by European Medicines Agency (EMA) to treat LHON. However better understanding of disease mechanisms and ongoing treatment trials are promising and brings hope for patients. In this article we report on a patient diagnosed with LHON harbouring rare m.11253T>C mutation in MT-ND4 gene, who experienced spontaneous visual recovery. In addition, we summarise clinical presentation, diagnostic features, and treatment.

Leber´s hereditary optic neuropathy: vision recovery due to spontaneous remission or Idebenone treatment outcome? - a case report / Neuropatia óptica hereditária da Leber: recuperação da visão devido a remissão espontânea ou resultado do tratamento com Idebenone? - um relato de caso

“…4,5 Besides the undeniable link to the mtDNA alterations, Leber´s Hereditary Optic Neuropathy has proven to be far more complex as a diseaseenvironmental triggers such as excessive smoking and alcohol consumption may start the disease on mutation carriers. 3 Other factor concerns the gender of patientssome studies present data on relation of hormonal diferences between male and female. The higher level of estrogen, for example, may be related to less cases of LHON affecting women, though they may be carriers of gene mutations.…”

“…Estrogen is also related to exert neuroprotective effect on retinal ganglion cells during heightenned cellular stress, which may explain more severe symptons on men compared to women. 3 There are few studies on Leber´s Hereditary Optic Neuropathy. Most of them are conducted on diferent countries.…”

Mitochondrial respiratory complexes: Significance in human mitochondrial disorders and cancers

“…Two of those, 13340T>C and 13379A>G, were in MT‐ND5 , while there was one mutation each in MT‐ND6 (14538A>G), MT‐ND3 (10350C>A), and MT‐ND1 (3632C>T) (Peverelli et al, 2021). Some other type of rather rare mutations linked to LHON are 1253T>C in MT‐ND4 (Liutkeviciene et al, 2021), 13345G>A in MT‐ND5 (Engvall et al, 2021), 3890G>A in MT‐ND1 (Vacchiano et al, 2021). Achilli et al reported a case study in which they identified nine rare mutations in MT‐ND1 (3700G>A,3733G>A‐C),4171C>A), MT‐ND4L (10663T> CA), and MT‐ND6 (14459G>A, 14495A>G, 14482C>A, and 14568C>T) (Achilli et al, 2012).…”