Influence of Mutation Type on Clinical Expression of Leber Hereditary Optic Neuropathy

Spruijt, Liesbeth; Kolbach, Dinanda N; Coo, I.F.M. de; Plomp, Astrid S.; Bauer, Noël; Smeets, H.; Die-Smulders, C.E.M. de

doi:10.1016/j.ajo.2005.11.007

Cited by 125 publications

(74 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Based on an analysis of the families collected by van Senus 16 in The Netherlands, a maximum prevalence, corrected for bias due to a high fraction of individuals from a m.14484T>C founder family, reached an estimate of 1:39,000. 17 A metaanalysis of the LHON prevalence in Europe arrived at a frequency of 1:45,000. 18 Thus, the prevalence of affected LHON patients in different European countries is of the same magnitude, and geographic differences seem mainly to be due to different representation of very large pedigrees mimicking founder effects.…”

Section: Prevalencementioning

confidence: 99%

Prevalence and Genetics of Leber Hereditary Optic Neuropathy in the Danish Population

Rosenberg

Nørby

Schwartz

et al. 2016

Invest. Ophthalmol. Vis. Sci.

View full text Add to dashboard Cite

PURPOSE. In Denmark, the occurrence of Leber hereditary optic neuropathy (LHON) has continuously been monitored since 1944. We provide here a summary of 70 years of data collection including registered lines and subjects by the end of 2012.METHODS. Affected individuals were identified from a national register of hereditary eye diseases at the National Eye Clinic (NEC), a tertiary low vision rehabilitation center for the entire Danish population. The assembling of LHON pedigrees was based on the reconstruction of published families and newly diagnosed cases from 1980 to 2012 identified in the files of NEC. Genealogic follow-up on the maternal ancestry of all affected individuals was performed to identify a possible relation to an already known maternal line. A full genotypic characterization of the nation-based LHON cohort is provided.RESULTS. Forty different lines were identified. The number of live affected individuals with a verified mitochondrial DNA mutation was 104 on January 1, 2013, which translates to a prevalence rate of 1:54,000 in the Danish population.CONCLUSIONS. Haplogroup distribution as well as mutational spectrum of the Danish LHON cohort do not deviate from those of other European populations. The genealogic follow-up reveals a relatively high turnover among families with approximately 15 newly affected families per century and the dying out of earlier maternal lines.

show abstract

Section: Prevalencementioning

confidence: 99%

Prevalence and Genetics of Leber Hereditary Optic Neuropathy in the Danish Population

Rosenberg

Nørby

Schwartz

et al. 2016

Invest. Ophthalmol. Vis. Sci.

View full text Add to dashboard Cite

show abstract

“…49 It has been recently shown that under specific circumstances, idebenone may have an effect on mitochondrial biogenesis, 50 but further research is warranted to further elucidate this. 35 Newman et al, 36 Lam et al 37 m.14484T>C 37%-71% Johns et al, 38 Mcmillan et al, 39 Spruijt et al 40 m.3460G>A 15%-25% Harding et al, 35 Spruijt et al, 40 Johns et al 41 idebenone for patients with LHON up to 5 years after clinical onset (NCT02774005). As a control group for the LEROS study, data are being collected in a CRS study ("Historical Case Record Survey of Visual Acuity Data from Patients with LHON"), which is an observational retrospective study of a cohort of patients with LHON who had not been treated with idebenone.…”

Section: Ideal Duration Of Treatment a Longer Treatment Periodmentioning

confidence: 99%

Use of Idebenone for the Treatment of Leber’s Hereditary Optic Neuropathy

Catarino

Klopstock

2017

Journal of Inborn Errors of Metabolism and Screening

View full text Add to dashboard Cite

Leber's hereditary optic neuropathy (LHON) is one of the most frequent mitochondrial disorders. It is caused by mutations in genes of the mitochondrial DNA coding for subunits of the respiratory chain and leads to severe bilateral vision loss, from which spontaneous recovery is infrequent. Retinal ganglion cells show a selective vulnerability to mitochondrial dysfunction in LHON. Idebenone is the first medication approved for LHON. It is a short-chain benzoquinone, which is an analogue of coenzyme Q10, but with distinct properties and mechanisms of action. Idebenone is a potent antioxidant and inhibitor of lipid peroxidation. Importantly, it facilitates electron flux directly to complex III, bypassing the dysfunctional complex I of the mitochondrial respiratory chain, thereby increasing adenosine triphosphate (ATP) production. In the Rescue of Hereditary Optic Disease Outpatient Study (RHODOS) randomized placebo-controlled clinical trial, 85 patients with LHON were enrolled, in the first 5 years after symptom onset, and randomized to either idebenone 900 mg/d for 6 months or placebo. Idebenone was well tolerated, and although the prespecified primary end point (best recovery in visual acuity [VA]) did not reach statistical significance, all secondary end points (change in best VA, change of VA of best eye at baseline, and change of VA in all eyes) showed a trend toward visual recovery in favor of idebenone. An increasing body of evidence shows that idebenone is effective and safe for the treatment of patients with LHON, including a large retrospective open-label study, several case reports and case series, an expanded access program, and ongoing post-authorization clinical studies. Here, we review the literature on idebenone for the treatment of patients with LHON.

show abstract

“…The chances of recovery depend on the patient's mutational status, the visual prognosis being poorest for the m.11778G[A mutation, highest for the m.14484T[C mutation, and intermediate for the m.3460G[A mutation. Positive prognostic factors for visual improvement are early age at onset and subacute presentation with slow progression [1][2][3].…”

Section: Commentmentioning

confidence: 99%

Topiramate and visual loss in a patient carrying a Leber hereditary optic neuropathy mutation

2011

View full text Add to dashboard Cite

We describe a 43-year-old patient who experienced visual loss 4 years after beginning antiepileptic therapy with topiramate. Ophthalmological and neurological examinations led to a preliminary diagnosis of bilateral toxic optic neuritis. Mitochondrial genome sequence analysis detected a Leber hereditary optic neuropathy 11778G>A mutation. The possibility that topiramate might favor a conversion disease, alerts physicians to seek a history of blindness in patients undergoing chronic antiepileptic therapy.

show abstract

Influence of Mutation Type on Clinical Expression of Leber Hereditary Optic Neuropathy

Cited by 125 publications

References 35 publications

Prevalence and Genetics of Leber Hereditary Optic Neuropathy in the Danish Population

Prevalence and Genetics of Leber Hereditary Optic Neuropathy in the Danish Population

Use of Idebenone for the Treatment of Leber’s Hereditary Optic Neuropathy

Topiramate and visual loss in a patient carrying a Leber hereditary optic neuropathy mutation

Contact Info

Product

Resources

About