Leber遺伝性視神経症認定基準 - nanbyou.or.jp

1 27 5 10 339 650-0017 7 5 1 ( 26 11 4 27 1 9 ) E-mail requests to Makoto Nakamura, Division of Ophthalmology, Department of Surgery Related, KobeUniversity Graduate School of Medicine. 7-5-1 Kusunoki-cho, Chuo-ku, kobe 650-0017, Japan(Received November 4, 2014 and accepted in revised form January 9, 2015)Designation criteria for Leber s hereditary opticneuropathy(LHON)have been established by aworking group for retino-choroidal and optic atrophyfunded by the Ministry of Health,Labor,and Welfare(MHLW)of Japan in collaboration with the JapaneseNeuro-ophthalmology criteria are com-posed of three major symptoms and three ancillarytest to the number and thecombination of these symptoms and findings,subjectsare classified intodefinite,probable, majorsymptoms include bilateral involvement with a time-lag,a papillomacular bundle atrophy,both character-istic optic disc findings at the acute theancillary testings,mitochondrial DNA mutationsspecific for LHON are detailed with a table listing themutation loci being enhance readers understanding of description of the major symptomsand ancillary test findings.

2 Explanatory remarks on11 parameters are establishmentof the criteria facilitates epidemiological survey ofLHON by MHLW and contributes to improvement ofwelfare for patients with LHON in JapanNippon Ganka Gakkai Zasshi( J Jpn Ophthalmol Soc)119 339-346, words Leber s hereditary optic neuropathy,Designation criteria,Intractable dis-ease,Mitochondrial DNA Leber 3 3 11 Leber ( 119 339-346 2015) Leber Makoto Nakamura1), Osamu Mimura2), Masato Wakakura3), Masaru Inatani4)Toru Nakazawa5)and Fumio Shiraga6)1)Division of Ophthalmology,Department of Surgery Related, kobe University Graduate School of Medicine2)Department of Ophthalmology,Hyogo Medical College3)Inouye Eye Hospital4)Department of Ophthalmology,Faculty of Medical Science,University of Fukui5)Department of Ophthalmology,Tohoku University Graduate School of Medicine6)Department of Ophthalmology,Okayama University Graduate School of MedicineAbstractReview ArticleDesignation Criteria for Leber s Hereditary Optic Neuropathy 1) 2) 3) 4) 5) 6) 1) 2) 3) 4) 5) 6)

3 Leber I Leber 1) 5) 2015 Leber Leber IILeber 1) 4) ) 1 ( 1A) ) 5) 8)( 1) 3,460 11,778 14,484 11,778 (G) (A) 90 6)7) computed tomography(CT) magnetic resonance imaging(MRI) 3) 3)( 1B) ) 1)2) 14,000 1 10 ( ) 9)10) ) (10 20 ) 1) 4) 1995 Leber 79 89 82 ( ) 7) 119 5 340 1 Leber A B ) 1) 4)7) 30 11)

4 10)12) ( ) 10 ) (rel-ative afferent pupillary defect) 13) 14) ) (critical flicker frequency) 12) Y magnocelullar ) (circum-papillaryretinalnervefiberlayer cpRNFL) 15) cpRNFL 16) cpRNFL 17) ) 3)4)10) 4) 5) Leber X parvocellular 3)4)10) ) 18) 19)20) (ragged red fiber) ) ( ) 2)3)10)11) 10)21) 10) Leber 3 10)22)( 1) 4)10)22) 1 Leber (ho-moplasmy) 3)4)10)23) 8,000 1 3 1 9)10) 50 10 20 ( 3,460 11,778 )

5 3,460 DNA K 11,778 14,484 J 10)21) 11,778 14,484 3) ( ) homoplas-my epigenetic Leber 3)10) X 24) 2)25) 26) 11) 10) Q10 ( ) 27)28) 29) (digital biochemicalinformation transfer and sensing compound) EPI-743 30) 10)31) 27 5 10 Leber 341 Leber (definiteLHON) 1 1) 2) (probableLHON) 1 1) 2) (possible LHON) 1 1) 2) (LHON carrier) 1 2) 2) 2) (1) 1 11) Leber 1) Leber 1) (2) 2) 9)

6 Leber Leber ( ) ( 4 ) 119 5 A C T A A m. 14482C A m. 14482C G m. 14495A G T T A A MTCO3 1 Leber DNA A CMTND4 MTND1 MTND mitochondrial nicotinamide adenine dinucleotide dehydrogenase subunit MTATP mitochondrial adenosine triphosphate MTCO mitochondrial cyto-chrome C oxidase MTCYB mitochondrial cytochrome b 2 Leber Leber 10 Table 1 A 22 C MTND4L ( 90 ) C T G C A A A A A T C A MTND1 ( 10 ) A.

7 5244G CMTND3 MTCYBMTND4 27 5 10 Leber 343 ) 1 3 2 2 3 (6 ) ) 4 9 3 2 4 1 2 2 3 1 ) 1 3 4 9 2 1 (ADL) 0 1 ( )2 ( )3 ( )4 ( ) 0 1 2 3 4 0 1 ( )2 ( )3 ( )4 ( ) 0 1 2 3 4 0 1 2 3 4 0 1 2 3 4 ( )0 1 1 2 1 1 3 1 1 4 1 2 0 1 ( )2 ( )3 ( )4 ( ) 0 1 2 3 4 3 ( MRC modified Medical Research Council scale)0 1 (MRC 4)2 (MRC 3)3 (MRC 2)4 (MRC 0 1) ( ICARS InternationalCooperativeAtaxiascale)0 1 2 ( )3 ( )

8 4 ( ) 0 1 (1 2km )2 ( )3 (100 400m )4 (10m ) ( )0 1 2 3 4 4 0 1 2 ( )3 TV 4 ADL 5 0 25dBHL ( )1 25 40dBHL( )2 40 70dBHL( )3 70 90dBHL( )4 90dBHL ( ) 500 1000 2000Hz ( ) 6 0 1 (EF 60 ) 2 EF 60 3 (EF 40 60 )4 7 0 1 50 90 2 30 50 3 10 30 4 10 8 0 1 2 3 4 9 0 1 AST ALT 2 AST ALT 3 AST ALT 2 20) (1) 1 (2)

9 MR CT MRI 1 ( 6 ) Q10 DNA DNA (1) 1 (2) 2 ( 3 ) (1) 1 (2) 1 ( 2 ) III 2015 1 ( 2)20) ( ) Leber Leber 2 1 (1) (2) 1 (