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- 1. フェニルケトン尿症の概要 overview of phenylketonuria
English Journal
- Characterization of transgenic Gfrp knock-in mice: implications for tetrahydrobiopterin in modulation of normal tissue radiation responses.
- Pathak R1, Pawar SA, Fu Q, Gupta PK, Berbée M, Garg S, Sridharan V, Wang W, Biju PG, Krager KJ, Boerma M, Ghosh SP, Cheema AK, Hendrickson HP, Aykin-Burns N, Hauer-Jensen M.Author information 11 Division of Radiation Health, University of Arkansas for Medical Sciences , Little Rock, Arkansas.AbstractAIMS: The free radical scavenger and nitric oxide synthase cofactor, 5,6,7,8-tetrahydrobiopterin (BH4), plays a well-documented role in many disorders associated with oxidative stress, including normal tissue radiation responses. Radiation exposure is associated with decreased BH4 levels, while BH4 supplementation attenuates aspects of radiation toxicity. The endogenous synthesis of BH4 is catalyzed by the enzyme guanosine triphosphate cyclohydrolase I (GTPCH1), which is regulated by the inhibitory GTP cyclohydrolase I feedback regulatory protein (GFRP). We here report and characterize a novel, Cre-Lox-driven, transgenic mouse model that overexpresses Gfrp.
- Antioxidants & redox signaling.Antioxid Redox Signal.2014 Mar 20;20(9):1436-46. doi: 10.1089/ars.2012.5025. Epub 2013 May 3.
- AIMS: The free radical scavenger and nitric oxide synthase cofactor, 5,6,7,8-tetrahydrobiopterin (BH4), plays a well-documented role in many disorders associated with oxidative stress, including normal tissue radiation responses. Radiation exposure is associated with decreased BH4 levels, while BH4
- PMID 23521531
- Sapropterin dihydrochloride use in pregnant women with phenylketonuria: An interim report of the PKU MOMS sub-registry.
- Grange DK1, Hillman RE2, Burton BK3, Yano S4, Vockley J5, Fong CT6, Hunt J7, Mahoney JJ7, Cohen-Pfeffer JL8; Phenylketonuria Demographics Outcomes and Safety (PKUDOS) registry; Maternal Phenylketonuria Observational Program (PKU MOMS) sub-registry.Author information 1Washington University School of Medicine, One Children's Place, NWT 9th Floor, St. Louis, MO 63110, USA.2University of Missouri Health Care, One Hospital Drive, University of Missouri, Columbia, MO 65212, USA.3Ann and Robert H. Lurie Children's Hospital of Chicago, 225 E. Chicago Ave., Box #59, Chicago, IL 60611-2605, USA.4Los Angeles County & University of Southern California Medical Center, 1801 Marengo Street, Rm 1G-24, Los Angeles, CA 90033, USA.5University of Pittsburgh School of Medicine, Children's Hospital of Pittsburgh, 4401 Penn Ave, Pittsburgh, PA 15224, USA; University of Pittsburgh Graduate School of Public Health, Pittsburgh, PA 15224, USA.6University of Rochester Medical Center, Clinic of Inherited Metabolic Disease, Box 777, Genetics 601, Elmwood Avenue, Rochester, NY 14642-8315, USA.7BioMarin Pharmaceutical Inc., 105 Digital Drive, Novato, CA 94949, USA.8BioMarin Pharmaceutical Inc., 105 Digital Drive, Novato, CA 94949, USA. Electronic address: JCohen@bmrn.com.AbstractFor pregnant women with phenylketonuria (PKU), maintaining blood phenylalanine (Phe)<360μmol/L is critical due to the toxicity of elevated Phe to the fetus. Sapropterin dihydrochloride (sapropterin) lowers blood Phe in tetrahydrobiopterin (BH4) responsive patients with PKU, in conjunction with a Phe-restricted diet, but clinical evidence supporting its use during pregnancy is limited. As of June 3, 2013, the Maternal Phenylketonuria Observational Program (PKU MOMS) sub-registry contained data from 21 pregnancies - in women with PKU who were treated with sapropterin either before (N=5) or during (N=16) pregnancy. Excluding data for spontaneous abortions (N=4), the data show that the mean of median blood Phe [204.7±126.6μmol/L (n=14)] for women exposed to sapropterin during pregnancy was 23% lower, and had a 58% smaller standard deviation, compared to blood Phe [267.4±300.7μmol/L (n=3)] for women exposed to sapropterin prior to pregnancy. Women on sapropterin during pregnancy experienced fewer blood Phe values above the recommended 360μmol/L threshold. When median blood Phe concentration was <360μmol/L throughout pregnancy, 75% (12/16) of pregnancy outcomes were normal compared to 40% (2/5) when median blood Phe was >360μmol/L. Severe adverse events identified by the investigators as possibly related to sapropterin use were premature labor (N=1) and spontaneous abortion (N=1) for the women and hypophagia for the offspring [premature birth (35w4d), N=1]. One congenital malformation (cleft palate) of unknown etiology was reported as unrelated to sapropterin. Although there is limited information regarding the use of sapropterin during pregnancy, these sub-registry data show that sapropterin was generally well-tolerated and its use during pregnancy was associated with lower mean blood Phe. Because the teratogenicity of elevated maternal blood Phe is without question, sapropterin should be considered as a treatment option in pregnant women with PKU who cannot achieve recommended ranges of blood Phe with dietary therapy alone.
- Molecular genetics and metabolism.Mol Genet Metab.2014 Mar 12. pii: S1096-7192(14)00088-2. doi: 10.1016/j.ymgme.2014.02.016. [Epub ahead of print]
- For pregnant women with phenylketonuria (PKU), maintaining blood phenylalanine (Phe)<360μmol/L is critical due to the toxicity of elevated Phe to the fetus. Sapropterin dihydrochloride (sapropterin) lowers blood Phe in tetrahydrobiopterin (BH4) responsive patients with PKU, in conjunction with a
- PMID 24667082
- Phenylketonuria Scientific Review Conference: State of the science and future research needs.
- Camp KM1, Parisi MA2, Acosta PB3, Berry GT4, Bilder DA5, Blau N6, Bodamer OA7, Brosco JP8, Brown CS9, Burlina AB10, Burton BK11, Chang CS12, Coates PM13, Cunningham AC14, Dobrowolski SF15, Ferguson JH16, Franklin TD17, Frazier DM18, Grange DK19, Greene CL20, Groft SC21, Harding CO22, Howell RR23, Huntington KL24, Hyatt-Knorr HD25, Jevaji IP26, Levy HL27, Lichter-Konecki U28, Lindegren ML29, Lloyd-Puryear MA30, Matalon K31, Macdonald A32, McPheeters ML33, Mitchell JJ34, Mofidi S35, Moseley KD36, Mueller CM37, Mulberg AE38, Nerurkar LS39, Ogata BN40, Pariser AR41, Prasad S42, Pridjian G43, Rasmussen SA44, Reddy UM45, Rohr FJ46, Singh RH47, Sirrs SM48, Stremer SE49, Tagle DA50, Thompson SM51, Urv TK52, Utz JR53, van Spronsen F54, Vockley J55, Waisbren SE56, Weglicki LS57, White DA58, Whitley CB59, Wilfond BS60, Yannicelli S61, Young JM62.Author information 1Office of Dietary Supplements, National Institutes of Health, Bethesda, MD 20982, USA. Electronic address: campkm@od.nih.gov.2Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA. Electronic address: parisima@mail.nih.gov.3Emory University, Atlanta, GA 30033, USA. Electronic address: pja1933@gmail.com.4Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA. Electronic address: gerard.berry@childrens.harvard.edu.5Department of Psychiatry, University of Utah, Salt Lake City, UT 84108, USA. Electronic address: deborah.bilder@hsc.utah.edu.6University Children's Hospital, Heidelberg, Germany; University Children's Hospital, Zürich, Switzerland. Electronic address: nenad.blau@med.uni-heidelberg.de.7University of Miami Miller School of Medicine, Miami, FL 33136, USA. Electronic address: obodamer@med.miami.edu.8University of Miami Mailman Center for Child Development, Miami, FL 33101, USA. Electronic address: jbrosco@med.miami.edu.9National PKU Alliance, USA. Electronic address: christine.brown@npkua.org.10University Hospital, 35128 Padova, Italy. Electronic address: alberto.burlina@unipd.it.11Ann and Robert H. Lurie Children's Hospital of Chicago, Chicago, IL 60611, USA. Electronic address: bburton@luriechildrens.org.12Agency for Healthcare Research and Quality, Rockville, MD 20850, USA. Electronic address: christine.chang@ahrq.hhs.gov.13Office of Dietary Supplements, National Institutes of Health, Bethesda, MD 20982, USA. Electronic address: coatesp@od.nih.gov.14Tulane University Medical School, Hayward Genetics Center, New Orleans, LA 70112, USA. Electronic address: acunnin@tulane.edu.15University of Pittsburgh, Pittsburgh, PA 15224, USA. Electronic address: dobrowolskis@upmc.edu.16Office of Rare Diseases Research, National Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, MD 20982, USA. Electronic address: jferg@helix.nih.gov.17National PKU Alliance, USA. Electronic address: tom.franklin@npkua.org.18University of North Carolina, Chapel Hill, NC 27599, USA. Electronic address: dianne_frazier@med.unc.edu.19Washington University School of Medicine, St. Louis Children's Hospital, St. Louis, MO 63110, USA. Electronic address: grange_d@kids.wustl.edu.20University of Maryland School of Medicine, Baltimore, MD 21201, USA. Electronic address: cgreene@peds.umaryland.edu.21Office of Rare Diseases Research, National Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, MD 20982, USA. Electronic address: stephen.groft@nih.gov.22Oregon Health & Science University, Portland, OR 97239, USA. Electronic address: hardingc@ohsu.edu.23University of Miami Miller School of Medicine, Miami, FL 33136, USA. Electronic address: rhowell@miami.edu.24Oregon Health & Science University, Portland, OR 97239, USA. Electronic address: huntingt@ohsu.edu.25Office of Rare Diseases Research, National Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, MD 20982, USA. Electronic address: henrietta.hyatt-knorr@nih.gov.26Office of Research on Women's Health, National Institutes of Health, Bethesda, MD 20817, USA. Electronic address: indira.jevaji@cms.hhs.gov.27Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA. Electronic address: harvey.levy@childrens.harvard.edu.28George Washington University, Children's National Medical Center, Washington, DC 20010, USA. Electronic address: ulichter@cnmc.org.29Vanderbilt University School of Medicine, Nashville TN 37203, USA. Electronic address: marylou.lindegren@vanderbilt.edu.30Office of Dietary Supplements, National Institutes of Health, Bethesda, MD 20982, USA. Electronic address: lloydpuryearma@od.nih.gov.31University of Houston, Houston, TX 77204, USA. Electronic address: kmatalon@uh.edu.32Birmingham Children's Hospital, Birmingham B4 6NH, UK. Electronic address: anita.macdonald@bch.nhs.uk.33Vanderbilt Evidence-based Practice Center, Institute for Medicine and Public Health, Nashville, TN 37203, USA. Electronic address: melissa.mcpheeters@vanderbilt.edu.34McGill University Health Center, Montreal, Quebec H3H 1P3, Canada. Electronic address: john.mitchell@muhc.mcgill.ca.35Maria Fareri Children's Hospital of Westchester Medical Center, Valhalla, NY 10595, USA. Electronic address: shideh_mofidi@nymc.edu.36University of Southern California Keck School of Medicine, Los Angeles, CA 90033, USA. Electronic address: kmoseley@usc.edu.37Office of Orphan Products Development, U.S. Food and Drug Administration, Silver Spring, MD 20993, USA. Electronic address: christine.mueller@nih.gov.38Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, MD 20993, USA. Electronic address: andrew.mulberg@fda.hhs.gov.39Office of Rare Diseases Research, National Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, MD 20982, USA. Electronic address: lnerurkar@gmail.com.40University of Washington, Seattle, WA 98195, USA. Electronic address: bogata@uw.edu.41Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, MD 20993, USA. Electronic address: anne.pariser@fda.hhs.gov.42BioMarin Pharmaceutical Inc., San Rafael, CA 94901, USA. Electronic address: sprasad@bmrn.com.43Tulane University Medical School, Hayward Genetics Center, New Orleans, LA 70112, USA. Electronic address: pridjian@tulane.edu.44Centers for Disease Control and Prevention, Atlanta, GA 30333, USA. Electronic address: skr9@cdc.gov.45Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA. Electronic address: reddyu@mail.nih.gov.46Boston Children's Hospital, Boston, MA 02115, USA. Electronic address: frances.rohr@childrens.harvard.edu.47Emory University, Atlanta, GA 30033, USA. Electronic address: rsingh@emory.edu.48Vancouver General Hospital, University of British Columbia, Vancouver V5Z 1M9, Canada. Electronic address: sandra.sirrs@vch.ca.49PKU & Allied Disorders of Wisconsin, Madison, WI 53705, USA. Electronic address: sstremer@yahoo.com.50National Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, MD 20892, USA. Electronic address: danilo.tagle@nih.gov.51The Children's Hospital at Westmead, Sydney, NSW 2145, Australia. Electronic address: sue.thompson@health.nsw.gov.au.52Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA. Electronic address: urvtiin@mail.nih.gov.53University of Minnesota, Minneapolis, MN 55455, USA. Electronic address: jutz1@fairview.org.54University of Groningen, University Medical Center of Groningen, Beatrix Children's Hospital, Netherlands. Electronic address: f.j.van.spronsen@umcg.nl.55University of Pittsburgh, Pittsburgh, PA 15224, USA. Electronic address: vockleyg@upmc.edu.56Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA. Electronic address: susan.waisbren@childrens.harvard.edu.57National Institute of Nursing Research, National Institutes of Health, Bethesda, MD 20892, USA. Electronic address: weglickils@mail.nih.gov.58Department of Psychology, Washington University, St. Louis, MO 63130, USA. Electronic address: dawhite@wustl.edu.59University of Minnesota, Minneapolis, MN 55455, USA. Electronic address: whitley@umn.edu.60Seattle Children's Research Institute, University of Washington School of Medicine, Seattle, WA 98101, USA. Electronic address: benjamin.wilfond@seattlechildrens.org.61Nutricia North America, Rockville, MD 20850, USA. Electronic address: steven.yannicelli@nutricia.com.62The Young Face, Facial Plastic and Reconstructive Surgery, Cumming, GA 30041, USA. Electronic address: jmichaelyoung@yahoo.com.AbstractNew developments in the treatment and management of phenylketonuria (PKU) as well as advances in molecular testing have emerged since the National Institutes of Health 2000 PKU Consensus Statement was released. An NIH State-of-the-Science Conference was convened in 2012 to address new findings, particularly the use of the medication sapropterin to treat some individuals with PKU, and to develop a research agenda. Prior to the 2012 conference, five working groups of experts and public members met over a 1-year period. The working groups addressed the following: long-term outcomes and management across the lifespan; PKU and pregnancy; diet control and management; pharmacologic interventions; and molecular testing, new technologies, and epidemiologic considerations. In a parallel and independent activity, an Evidence-based Practice Center supported by the Agency for Healthcare Research and Quality conducted a systematic review of adjuvant treatments for PKU; its conclusions were presented at the conference. The conference included the findings of the working groups, panel discussions from industry and international perspectives, and presentations on topics such as emerging treatments for PKU, transitioning to adult care, and the U.S. Food and Drug Administration regulatory perspective. Over 85 experts participated in the conference through information gathering and/or as presenters during the conference, and they reached several important conclusions. The most serious neurological impairments in PKU are preventable with current dietary treatment approaches. However, a variety of more subtle physical, cognitive, and behavioral consequences of even well-controlled PKU are now recognized. The best outcomes in maternal PKU occur when blood phenylalanine (Phe) concentrations are maintained between 120 and 360μmol/L before and during pregnancy. The dietary management treatment goal for individuals with PKU is a blood Phe concentration between 120 and 360μmol/L. The use of genotype information in the newborn period may yield valuable insights about the severity of the condition for infants diagnosed before maximal Phe levels are achieved. While emerging and established genotype-phenotype correlations may transform our understanding of PKU, establishing correlations with intellectual outcomes is more challenging. Regarding the use of sapropterin in PKU, there are significant gaps in predicting response to treatment; at least half of those with PKU will have either minimal or no response. A coordinated approach to PKU treatment improves long-term outcomes for those with PKU and facilitates the conduct of research to improve diagnosis and treatment. New drugs that are safe, efficacious, and impact a larger proportion of individuals with PKU are needed. However, it is imperative that treatment guidelines and the decision processes for determining access to treatments be tied to a solid evidence base with rigorous standards for robust and consistent data collection. The process that preceded the PKU State-of-the-Science Conference, the conference itself, and the identification of a research agenda have facilitated the development of clinical practice guidelines by professional organizations and serve as a model for other inborn errors of metabolism.
- Molecular genetics and metabolism.Mol Genet Metab.2014 Mar 6. pii: S1096-7192(14)00085-7. doi: 10.1016/j.ymgme.2014.02.013. [Epub ahead of print]
- New developments in the treatment and management of phenylketonuria (PKU) as well as advances in molecular testing have emerged since the National Institutes of Health 2000 PKU Consensus Statement was released. An NIH State-of-the-Science Conference was convened in 2012 to address new findings, part
- PMID 24667081
Japanese Journal
- テトラヒドロビオプテリンによるフェニルケトン尿症の新しい治療法
- 呉 繁夫
- ビタミン 84(12), 610-611, 2010-12-25
- NAID 110008006994
- 企業リポート 日本発オーファンドラッグ「ビオプテン」--高フェニルアラニン血症治療薬の国内開発・効能追加と海外展開に対するアスビオファーマの取り組み
- 亀位 勝秀,末澤 克己
- 生産と技術 61(2), 48-51, 2009
- NAID 40016873425
- 塩酸サプロブテリン(SUNO588)のラットにおける体内動態 (Studies on metabolism and disposition of sapropterin hydrochloride (SUN 0588) L-erythro-tetrahydrobiopterin hydrochloride in rats)
- 林敏郎
- 基礎と臨床 26, 3471-3495, 1992
- NAID 80006592203
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