FOLKSHÖGSKOLAN SÖDERTÄLJE

Transkript

1 FOLKSHÖGSKOLAN SÖDERTÄLJE

2 LEBER S HEREDITARY OPTIC NEUROPATHY (LHON) THOMAS ROSENBERG NATIONAL EYE CLINIC FOR THE VISUALLY IMPAIRED

3 NAVNET THEODOR KARL GUSTAV VON LEBER ( ) GÖTTINGEN Über hereditäre und congenital angelegte Sehnervenleiden (1871) JOURNAL 1874

4 SYNSNERVEN ANGRIBES

5 HVAD SKER DER MED SYNET? AKUT FASE KRONISK FASE

6 ANDRE SYMPTOMER NERVESYSTEM CENTRALT PERIFERT HJERTE

7 ARVEFORHOLD TRE GÅDER GÅDE NR. 1 SKÆV KØNSFORDELING

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

9 GÅDE NR. 3 LHON RAMMER KUN NOGLE ARVEBÆRERE NEDSAT PENETRANS

10 SLÆGTSFORSKER PÅ HÅRDT ARBEJDE

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

12 TRE HYPPIGE MTDNA MUTATIONER MEDFØRER NEDSAT PRODUKTION AF ENERGI (ATP) ND1 ND4 (WALLACE) ND6 COMPLEX 1 NADH:UBIQUINON OXIDOREDUCTASE CoQ10 IDEBENONE

13 ATP PRODUKTION 75 KG/DØGN

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

15 Diagnosis HETEROPLASMI Clinical features Familial occurrence in maternally related lines Mutation analysis Differential diagnoses optic neuritis (MS), tobacco-alcohol amblyopia, neuroretinitis, intracranial pathology, 75% dominant infantile optic atrophy, other hereditary optical neuropathies (Behr syndrome, X-linked spastic paraplegia, hereditary ataxia, Wolfram NYOPSTÅET syndrome) MUTATION? 32% mutant DNA

16 HAPLOTYPER MTDNA VARIATIONER 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)

17 SYGDOMS MEKANISME ØGET ENERGIBEHOV VED SYGDOM OG ULYKKER NEDSAT ATP PRODUKTION VED MILJØBELASTNING TOBAKSRYGNING!

18 Diagnosis Clinical features Familial occurrence in maternally related lines Mutation analysis Differential diagnoses optic neuritis (MS), tobacco-alcohol amblyopia, neuroretinitis, GENETISK RÅDGIVNING intracranial pathology, dominant LIVSTIDS infantile RISIKO optic MÆND atrophy, 50% other hereditary optical KVINDER neuropathies 10% (Behr syndrome, X-linked spastic paraplegia, hereditary ataxia, Wolfram syndrome)

19 Diagnosis FOREKOMST (PRÆVALENS) Clinical features Familial DANMARK occurrence in maternally related lines Mutation analysis 2002: 113 PERSONER/34 FAMILIER ~ 2.1/ ~ 1: Differential diagnoses 2013 : 109 PERSONER/44 FAMILIER optic neuritis ~ 1,9/ (MS), tobacco-alcohol ~ 1: amblyopia, neuroretinitis, intracranial pathology, dominant infantile optic atrophy, other FINLAND hereditary optical neuropathies ~ 1: (Behr NØ syndrome, ENGLAND X-linked spastic ~ 1: paraplegia, hereditary ataxia, Wolfram syndrome)

20 Diagnosis Clinical features Familial occurrence in maternally related lines Mutation analysis DEBUTALDER Differential diagnoses 60 Females % 50 optic neuritis (MS), tobacco-alcohol amblyopia, Males 40 neuroretinitis, intracranial pathology, 30 dominant 20 infantile optic atrophy, 10 other hereditary optical neuropathies 0 Age at onset (Behr syndrome, X-linked spastic paraplegia, hereditary ataxia, Wolfram syndrome)

21 Diagnosis MUTATIONS FORDELING PÅ Clinical FAMILIER features Familial occurrence in maternally related lines Mutation 27 ND4/11778 analysis (68%) 6 ND1/3460 (15%) 7 ND6/14484 (18%) Differential diagnoses optic neuritis (MS), tobacco-alcohol amblyopia, MUTATIONS FORDELING PÅ neuroretinitis, KØN intracranial pathology, dominant infantile optic atrophy, 78 ND4 (63 M/15K) other 16 hereditary ND1 (12M/ optical 4K) neuropathies (Behr syndrome, X-linked spastic paraplegia, 10 ND6 ( 7M/ 3K) hereditary ataxia, Wolfram syndrome)

22 Diagnosis TAK FOR JERES INTERESSE 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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