Lebersche hereditäre Optikusneuropathie – Klinik, Genetik, therapeutische Optionen

Zusammenfassung

Die Lebersche hereditäre Optikusneuropathie ist eine seltene erbliche Erkrankung der retinalen Ganglienzellen und führt innerhalb von Wochen oder Monaten zu einer meist anhaltenden hochgradigen beidseitigen Visusminderung. Männer erkranken sehr viel häufiger als Frauen, das Erkrankungsalter liegt meist zwischen dem 15. und 35. Lebensjahr. Ursächlich sind Punktmutationen der mitochondrialen DNA. Bei der Erkrankung liegt eine unvollständige Penetranz vor, d. h. es erkranken keineswegs alle Personen, die eine Mutation tragen. Das klinische Erscheinungsbild ist relativ uniform, Erkrankungsbeginn, Schweregrad und Prognose können aber auch innerhalb einer Familie variabel sein. Als Erklärung für die unvollständige Penetranz, die Bevorzugung des männlichen Geschlechts und die interindividuelle und intrafamiliäre Variabilität werden Umweltfaktoren sowie hormonelle und anatomische Besonderheiten diskutiert. Zigarettenrauchen und übermäßiger Alkoholkonsum konnten in einer großen epidemiologischen Studie als Risikofaktoren für ein erhöhtes Erkrankungsrisiko identifiziert werden. Daneben gibt es Hinweise, dass sekundäre genetische Faktoren wie das Vorliegen einer bestimmten mitochondrialen Haplogruppe und Veränderungen in Suszeptibilitätsgenen der nukleären DNA das Erkrankungsrisiko mitbeeinflussen. Klinisch findet sich bei der Erkrankung charakteristischerweise ein zentraler Gesichtsfeldausfall, eine Farbsinnstörung und fundoskopisch in der akuten Phase in den meisten Fällen eine peripapilläre Mikroangiopathie. Üblicherweise pendelt sich die Sehschärfe nach einigen Monaten auf einem niedrigen Niveau meist um einen durchschnittlichen Endvisus unter 0,1 ein und bessert sich in den meisten Fällen nicht mehr signifikant. Selten kann es jedoch im Verlauf zu einer meist nur partiellen Erholung des Visus kommen, wobei die Wahrscheinlichkeit dieses günstigen Verlaufs von der vorliegenden Mutation abhängt. Zur Diagnosestellung erforderlich ist neben ophthalmologischen Untersuchungen und der Erhebung einer ausführlichen Familienanamnese eine genetische Untersuchung der mitochondrialen DNA. Eine gesicherte kausale Therapie existiert bislang nicht, eine Therapieoption in der Frühphase der Erkrankung stellt die Gabe des Coenzym Q10-Abkömmlings Idebenone dar.

Abstract

Leberʼs hereditary optic neuropathy is a rare genetic disorder affecting the retinal ganglion cells leading to a persistent severe bilateral loss of visual acuity within weeks or months. Males are much more likely to be affected than females, disease onset in most cases takes place between age 15 and 35 years. The disease is caused by point mutations in the mitochondrial DNA. The penetrance of the disease is incomplete, i.e., not all mutation carriers develop clinical symptoms. The phenotype is relatively uniform, but age at onset, severity and prognosis may vary even within the same family. Environmental and endocrine factors, optic disc anatomy as well as mitochondrial and nuclear genetic factors are discussed to influence penetrance as well as interindividual and intrafamilial variability. However, only cigarette smoking and excessive alcohol consumption have been shown to trigger disease onset. The disease is characterised by a central visual field defect, impaired colour vision and fundoscopically a peripapillary microangiopathy in the acute phase. Most patients end up after some months with a severe visual loss below 0.1 and in most cases there is no significant improvement of visual acuity in the course. In rare cases patients experience a mostly partial visual recovery which depends on the type of mutation. For confirmation of the diagnosis a detailed ophthalmological examination with fundoscopy, family history and genetic analysis of the mitochondrial DNA is needed. To date, there is no proven causal therapy, but at early disease stages treatment with idebenone can be tried.

Schlüsselwörter

Genetik - Lebersche hereditäre Optikus-Neuropathie - LHON - mitochondriale Erkrankung

Key words

Genetics - Leberʼs hereditary optic neuropathy - LHON - mitochondrial disease

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