folkshÖgskolan sÖdertÄlje 25.10€¦ · optic neuritis (ms), tobacco-alcohol amblyopia,...
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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)
0
10
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40
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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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