タイトル厚生労働科学研究費補助金（難治性疾患克服研究事業）「Menkes 病・occipital horn 症候群の実態調査、早期診断基準確立、治療法開発に関する研究」平成23-24年度 総合研究報告書

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厚生労働科学研究費補助金（難治性疾患克服研究事業）「Menkes 病・occipital horn 症候群の実態調査、早期診断基準確立、治療法開発に関する研究」平成23-24年度 総合研究報告書

Y.-H. Gu et al. / Brain & Development 34 (2012) 746?749 749Table 2Median age (range) at onset, diagnosis, start of parenteral copper histidine treatment, at death and cause of death in MNK patients who had died.CongenitalmalformationMedian age (range) monthsAtonset *Atdiagnosis *At start oftreatment withparenteral copperhistidine *7.0(3.0?15.0)(n = 13)Atdeath **Of alivepatients(as of August 31,2009)68.5(n =1)Cause of death (number of patients)Yes(n = 13) aNo(n = 21)2.0(0.0?9.0)(n = 13)2.5(0.0?6.0)(n = 18)6.0(3.0?12.0)(n = 12)4.5(0.0?33.0)(n = 18)6.5(0.5?34.0)(n = 19)32.5(13.0?186.0)(n = 11)49.5(38.0?97.0)(n =8)42.0(17.0?104.0)(n =9)Infectious disease (4); Infectious diseaseand hemorrhage (1); sudden death (3);bladder hemorrhage (1); stomachhemorrhage (1); unknown (2); (n = 12)Infectious disease (5); central apnea (2);respiratory failure (1); rupture ofabdominal aorta (1); sputum obliterationin cannula (1); unknown (1); (n = 11)aData from patients who received prenatal diagnoses were excluded, with the exception of data pertaining to median age at death and cause ofdeath in patients with CMs.*P > 0.05, Mann?Whitney U test.**P < 0.05, Mann?Whitney U test.MNK patients may provide some clues regarding thepathological causes of MNK. However, even if patients1?5 had the same CM in Table 1, that is, a high archedpalate, mutations in their ATP7A genes were not consistent.Therefore, there was no association between CMsand mutations in the ATP7A gene.AcknowledgementsThis study was supported by the Japan Foundationfor Pediatric Research 2009, the Mother and ChildHealth Foundation of Japan, and Specified DiseaseTreatment Research Program of Ministry of Health, Labourand Welfare of Japan (H23/nanchi/ippan/091).References[1] Tonnesen T, Kleijer WJ, Horn N. Incidence of Menkes disease.Hum Genet 1991;86:408?10.[2] Gu YH, Kodama H, Shiga K, Nakata S, Yanagawa Y, Ozawa H.A survey of Japanese patients with Menkes disease from 1990 to2003: incidence and early signs before typical symptomatic onset,pointing the way to earlier diagnosis. J Inherit Metab Dis2005;28:473?8.[3] Sarkar B, Lingertat-Walsh K, Clarke JT. Copper-histidinetherapy for Menkes disease. J Pediatr 1993;123:828?30.[4] Chelly J, Tumer Z, Tonnesen T, Petterson A, Ishikawa-Brush Y,Tommerup N, et al. Isolation of a candidate gene for Menkesdisease that encodes a potential heavy metal binding protein. NatGenet 1993;3:14?9.[5] Mercer JF, Livingston J, Hall B, Paynter JA, Begy C, ChandrasekharappaS, et al. Isolation of a partial candidate gene forMenkes disease by positional cloning. Nat Genet 1993;3:20?5.[6] Vulpe C, Levinson B, Whitney S, Packman S, Gitschier J.Isolation of a candidate gene for Menkes disease and evidencethat it encodes a copper-transporting ATPase. Nat Genet1993;3:7?13.[7] Gu YH, Kodama H, Murata Y, Mochizuki D, Yanagawa Y,Ushijima H, et al. ATP7A gene mutations in 16 patients withMenkes disease and a patient with occipital horn syndrome. Am JMed Genet 2001;99:217?22.[8] Gu YH, Kodama H, Sato E, Mochizuki D, Yanagawa Y,Takayanagi M, et al. Prenatal diagnosis of Menkes disease bygenetic analysis and copper measurement. Brain Dev2002;24:715?8.[9] Gu YH. 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