folkshÖgskolan sÖdertÄlje 25.10€¦ · optic neuritis (ms), tobacco-alcohol amblyopia,...

FOLKSHÖGSKOLAN SÖDERTÄLJE

25.10.2013

LEBER’S HEREDITARY OPTIC NEUROPATHY (LHON)

THOMAS ROSENBERG NATIONAL EYE CLINIC FOR THE VISUALLY IMPAIRED

THEODOR KARL GUSTAV VON LEBER (1840-1917) GÖTTINGEN Über hereditäre und congenital angelegte Sehnervenleiden (1871)

JOURNAL 1874

NAVNET

SYNSNERVEN ANGRIBES

AKUT FASE 03.1993

KRONISK FASE 01.1994

HVAD SKER DER MED SYNET?

ANDRE SYMPTOMER

NERVESYSTEM CENTRALT PERIFERT HJERTE

ARVEFORHOLD TRE GÅDER

GÅDE NR. 1 SKÆV KØNSFORDELING

GÅDE NR. 2 KVINDER FØRER ARVEANLÆGGET VIDERE TIL ALLE DERES BØRN, MÆND KAN IKKE VIDEREGIVE LHON

GÅDE NR. 3

LHON RAMMER KUN NOGLE ARVEBÆRERE NEDSAT PENETRANS

SLÆGTSFORSKER PÅ HÅRDT ARBEJDE

ÅRSAG: MITOKONDRIEL ARV 1988: MITOKONDRIE MUTATION OG LØSNING PÅ GÅDE NR 3

TRE HYPPIGE MTDNA MUTATIONER MEDFØRER NEDSAT PRODUKTION AF ENERGI (ATP)

ND1 ND4 (WALLACE) ND6

COMPLEX 1 NADH:UBIQUINON OXIDOREDUCTASE

CoQ10 IDEBENONE

ATP PRODUKTION 75 KG/DØGN

HVORDAN OPSTÅR LHON? OG HVORFOR UDVIKLER SYGDOMMEN SIG FORSKELLIGT FRA PERSON TIL PERSON?

Diagnosis Clinical features Familial occurrence in maternally related lines Mutation analysis Differential diagnoses optic neuritis (MS), tobacco-alcohol amblyopia, neuroretinitis, intracranial pathology, dominant infantile optic atrophy, other hereditary optical neuropathies (Behr syndrome, X-linked spastic paraplegia, hereditary ataxia, Wolfram syndrome)

HETEROPLASMI

32% mutant DNA

75%

NYOPSTÅET MUTATION ?

Diagnosis Clinical features Familial occurrence in maternally related lines Mutation analysis Differential diagnoses optic neuritis (MS), tobacco-alcohol amblyopia, neuroretinitis, intracranial pathology, dominant infantile optic atrophy, other hereditary optical neuropathies (Behr syndrome, X-linked spastic paraplegia, hereditary ataxia, Wolfram syndrome)

HAPLOTYPER - MTDNA VARIATIONER

SYGDOMS MEKANISME

• ØGET ENERGIBEHOV VED SYGDOM OG ULYKKER • NEDSAT ATP PRODUKTION VED MILJØBELASTNING TOBAKSRYGNING!

Diagnosis Clinical features Familial occurrence in maternally related lines Mutation analysis Differential diagnoses optic neuritis (MS), tobacco-alcohol amblyopia, neuroretinitis, intracranial pathology, dominant infantile optic atrophy, other hereditary optical neuropathies (Behr syndrome, X-linked spastic paraplegia, hereditary ataxia, Wolfram syndrome)

GENETISK RÅDGIVNING LIVSTIDS RISIKO MÆND 50% KVINDER 10%

Diagnosis Clinical features Familial occurrence in maternally related lines Mutation analysis Differential diagnoses optic neuritis (MS), tobacco-alcohol amblyopia, neuroretinitis, intracranial pathology, dominant infantile optic atrophy, other hereditary optical neuropathies (Behr syndrome, X-linked spastic paraplegia, hereditary ataxia, Wolfram syndrome)

FOREKOMST (PRÆVALENS) DANMARK 2002: 113 PERSONER/34 FAMILIER

~ 2.1/100.000 ~ 1:47.500

2013 : 109 PERSONER/44 FAMILIER ~ 1,9/100.000 ~ 1:51.000

FINLAND ~ 1:50.000 NØ ENGLAND ~ 1:25.000

Diagnosis Clinical features Familial occurrence in maternally related lines Mutation analysis Differential diagnoses optic neuritis (MS), tobacco-alcohol amblyopia, neuroretinitis, intracranial pathology, dominant infantile optic atrophy, other hereditary optical neuropathies (Behr syndrome, X-linked spastic paraplegia, hereditary ataxia, Wolfram syndrome)

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10

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50

60

70

80

90

100

0-4 5-9 10-14 15-19 20-24 25-29 30-34 35-39 40-44 45-49 50-54 55-59 60-64 65-69 70-74

%

Age at onset

Females

Males

DEBUTALDER

Diagnosis Clinical features Familial occurrence in maternally related lines Mutation analysis Differential diagnoses optic neuritis (MS), tobacco-alcohol amblyopia, neuroretinitis, intracranial pathology, dominant infantile optic atrophy, other hereditary optical neuropathies (Behr syndrome, X-linked spastic paraplegia, hereditary ataxia, Wolfram syndrome)

MUTATIONS FORDELING PÅ FAMILIER 27 ND4/11778 (68%) 6 ND1/3460 (15%) 7 ND6/14484 (18%)

MUTATIONS FORDELING PÅ KØN 78 ND4 (63 M/15K) 16 ND1 (12M/ 4K) 10 ND6 ( 7M/ 3K)

Diagnosis Clinical features Familial occurrence in maternally related lines Mutation analysis Differential diagnoses optic neuritis (MS), tobacco-alcohol amblyopia, neuroretinitis, intracranial pathology, dominant infantile optic atrophy, other hereditary optical neuropathies (Behr syndrome, X-linked spastic paraplegia, hereditary ataxia, Wolfram syndrome)

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