Mol Genet Metab. 2014 Mar 6. pii: S1096-7192(14)00085-7. doi: 10.1016/j.ymgme.2014.02.013. [Epub ahead of print]
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.
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, 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.
Copyright © 2014. Published by Elsevier Inc. All rights reserved.
Glycomacropeptide, Hyperphenylalaninemia, Large neutral amino acids, Maternal PKU, Phenylketonuria, Sapropterin
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