Phenylketonuria scientific review conference: State of the science and future research needs

Kathryn M. Camp, Melissa A. Parisi, Phyllis B. Acosta, Gerard T. Berry, Deborah A. Bilder, Nenad Blau, Olaf A. Bodamer, Jeffrey P Brosco, Christine S. Brown, Alberto B. Burlina, Barbara K. Burton, Christine S. Chang, Paul M. Coates, Amy C. Cunningham, Steven F. Dobrowolski, John H. Ferguson, Thomas D. Franklin, Dianne M. Frazier, Dorothy K. Grange, Carol L. GreeneStephen C. Groft, Cary O. Harding, R. Howell, Kathleen L. Huntington, Henrietta D. Hyatt-Knorr, Indira P. Jevaji, Harvey L. Levy, Uta Lichter-Konecki, Mary Lou Lindegren, Michele A. Lloyd-Puryear, Kimberlee Matalon, Anita MacDonald, Melissa L. McPheeters, John J. Mitchell, Shideh Mofidi, Kathryn D. Moseley, Christine M. Mueller, Andrew E. Mulberg, Lata S. Nerurkar, Beth N. Ogata, Anne R. Pariser, Suyash Prasad, Gabriella Pridjian, Sonja A. Rasmussen, Uma M. Reddy, Frances J. Rohr, Rani H. Singh, Sandra M. Sirrs, Stephanie E. Stremer, Danilo A. Tagle, Susan M. Thompson, Tiina K. Urv, Jeanine R. Utz, Francjan van Spronsen, Jerry Vockley, Susan E. Waisbren, Linda S. Weglicki, Desirée A. White, Chester B. Whitley, Benjamin S. Wilfond, Steven Yannicelli, Justin M. Young

Research output: Contribution to journalArticle

103 Citations (Scopus)

Abstract

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 360. μmol/L before and during pregnancy. The dietary management treatment goal for individuals with PKU is a blood Phe concentration between 120 and 360. μmol/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.

Original languageEnglish
Pages (from-to)87-122
Number of pages36
JournalMolecular Genetics and Metabolism
Volume112
Issue number2
DOIs
StatePublished - Jan 1 2014

Fingerprint

Phenylketonurias
Phenylalanine
Blood
Testing
Nutrition
Metabolism
Health
Therapeutics
Pharmaceutical Preparations
Industry
Maternal Phenylketonuria
Research
Inborn Errors Metabolism
Pregnancy
Internationality
sapropterin
Evidence-Based Practice
Health Services Research
National Institutes of Health (U.S.)
Genetic Association Studies

Keywords

  • Glycomacropeptide
  • Hyperphenylalaninemia
  • Large neutral amino acids
  • Maternal PKU
  • Phenylketonuria
  • Sapropterin

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Genetics
  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

Cite this

Camp, K. M., Parisi, M. A., Acosta, P. B., Berry, G. T., Bilder, D. A., Blau, N., ... Young, J. M. (2014). Phenylketonuria scientific review conference: State of the science and future research needs. Molecular Genetics and Metabolism, 112(2), 87-122. https://doi.org/10.1016/j.ymgme.2014.02.013

Phenylketonuria scientific review conference : State of the science and future research needs. / Camp, Kathryn M.; Parisi, Melissa A.; Acosta, Phyllis B.; Berry, Gerard T.; Bilder, Deborah A.; Blau, Nenad; Bodamer, Olaf A.; Brosco, Jeffrey P; Brown, Christine S.; Burlina, Alberto B.; Burton, Barbara K.; Chang, Christine S.; Coates, Paul M.; Cunningham, Amy C.; Dobrowolski, Steven F.; Ferguson, John H.; Franklin, Thomas D.; Frazier, Dianne M.; Grange, Dorothy K.; Greene, Carol L.; Groft, Stephen C.; Harding, Cary O.; Howell, R.; Huntington, Kathleen L.; Hyatt-Knorr, Henrietta D.; Jevaji, Indira P.; Levy, Harvey L.; Lichter-Konecki, Uta; Lindegren, Mary Lou; Lloyd-Puryear, Michele A.; Matalon, Kimberlee; MacDonald, Anita; McPheeters, Melissa L.; Mitchell, John J.; Mofidi, Shideh; Moseley, Kathryn D.; Mueller, Christine M.; Mulberg, Andrew E.; Nerurkar, Lata S.; Ogata, Beth N.; Pariser, Anne R.; Prasad, Suyash; Pridjian, Gabriella; Rasmussen, Sonja A.; Reddy, Uma M.; Rohr, Frances J.; Singh, Rani H.; Sirrs, Sandra M.; Stremer, Stephanie E.; Tagle, Danilo A.; Thompson, Susan M.; Urv, Tiina K.; Utz, Jeanine R.; van Spronsen, Francjan; Vockley, Jerry; Waisbren, Susan E.; Weglicki, Linda S.; White, Desirée A.; Whitley, Chester B.; Wilfond, Benjamin S.; Yannicelli, Steven; Young, Justin M.

In: Molecular Genetics and Metabolism, Vol. 112, No. 2, 01.01.2014, p. 87-122.

Research output: Contribution to journalArticle

Camp, KM, Parisi, MA, Acosta, PB, Berry, GT, Bilder, DA, Blau, N, Bodamer, OA, Brosco, JP, Brown, CS, Burlina, AB, Burton, BK, Chang, CS, Coates, PM, Cunningham, AC, Dobrowolski, SF, Ferguson, JH, Franklin, TD, Frazier, DM, Grange, DK, Greene, CL, Groft, SC, Harding, CO, Howell, R, Huntington, KL, Hyatt-Knorr, HD, Jevaji, IP, Levy, HL, Lichter-Konecki, U, Lindegren, ML, Lloyd-Puryear, MA, Matalon, K, MacDonald, A, McPheeters, ML, Mitchell, JJ, Mofidi, S, Moseley, KD, Mueller, CM, Mulberg, AE, Nerurkar, LS, Ogata, BN, Pariser, AR, Prasad, S, Pridjian, G, Rasmussen, SA, Reddy, UM, Rohr, FJ, Singh, RH, Sirrs, SM, Stremer, SE, Tagle, DA, Thompson, SM, Urv, TK, Utz, JR, van Spronsen, F, Vockley, J, Waisbren, SE, Weglicki, LS, White, DA, Whitley, CB, Wilfond, BS, Yannicelli, S & Young, JM 2014, 'Phenylketonuria scientific review conference: State of the science and future research needs', Molecular Genetics and Metabolism, vol. 112, no. 2, pp. 87-122. https://doi.org/10.1016/j.ymgme.2014.02.013
Camp, Kathryn M. ; Parisi, Melissa A. ; Acosta, Phyllis B. ; Berry, Gerard T. ; Bilder, Deborah A. ; Blau, Nenad ; Bodamer, Olaf A. ; Brosco, Jeffrey P ; Brown, Christine S. ; Burlina, Alberto B. ; Burton, Barbara K. ; Chang, Christine S. ; Coates, Paul M. ; Cunningham, Amy C. ; Dobrowolski, Steven F. ; Ferguson, John H. ; Franklin, Thomas D. ; Frazier, Dianne M. ; Grange, Dorothy K. ; Greene, Carol L. ; Groft, Stephen C. ; Harding, Cary O. ; Howell, R. ; Huntington, Kathleen L. ; Hyatt-Knorr, Henrietta D. ; Jevaji, Indira P. ; Levy, Harvey L. ; Lichter-Konecki, Uta ; Lindegren, Mary Lou ; Lloyd-Puryear, Michele A. ; Matalon, Kimberlee ; MacDonald, Anita ; McPheeters, Melissa L. ; Mitchell, John J. ; Mofidi, Shideh ; Moseley, Kathryn D. ; Mueller, Christine M. ; Mulberg, Andrew E. ; Nerurkar, Lata S. ; Ogata, Beth N. ; Pariser, Anne R. ; Prasad, Suyash ; Pridjian, Gabriella ; Rasmussen, Sonja A. ; Reddy, Uma M. ; Rohr, Frances J. ; Singh, Rani H. ; Sirrs, Sandra M. ; Stremer, Stephanie E. ; Tagle, Danilo A. ; Thompson, Susan M. ; Urv, Tiina K. ; Utz, Jeanine R. ; van Spronsen, Francjan ; Vockley, Jerry ; Waisbren, Susan E. ; Weglicki, Linda S. ; White, Desirée A. ; Whitley, Chester B. ; Wilfond, Benjamin S. ; Yannicelli, Steven ; Young, Justin M. / Phenylketonuria scientific review conference : State of the science and future research needs. In: Molecular Genetics and Metabolism. 2014 ; Vol. 112, No. 2. pp. 87-122.
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abstract = "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 360. μmol/L before and during pregnancy. The dietary management treatment goal for individuals with PKU is a blood Phe concentration between 120 and 360. μmol/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.",
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T1 - Phenylketonuria scientific review conference

T2 - State of the science and future research needs

AU - Camp, Kathryn M.

AU - Parisi, Melissa A.

AU - Acosta, Phyllis B.

AU - Berry, Gerard T.

AU - Bilder, Deborah A.

AU - Blau, Nenad

AU - Bodamer, Olaf A.

AU - Brosco, Jeffrey P

AU - Brown, Christine S.

AU - Burlina, Alberto B.

AU - Burton, Barbara K.

AU - Chang, Christine S.

AU - Coates, Paul M.

AU - Cunningham, Amy C.

AU - Dobrowolski, Steven F.

AU - Ferguson, John H.

AU - Franklin, Thomas D.

AU - Frazier, Dianne M.

AU - Grange, Dorothy K.

AU - Greene, Carol L.

AU - Groft, Stephen C.

AU - Harding, Cary O.

AU - Howell, R.

AU - Huntington, Kathleen L.

AU - Hyatt-Knorr, Henrietta D.

AU - Jevaji, Indira P.

AU - Levy, Harvey L.

AU - Lichter-Konecki, Uta

AU - Lindegren, Mary Lou

AU - Lloyd-Puryear, Michele A.

AU - Matalon, Kimberlee

AU - MacDonald, Anita

AU - McPheeters, Melissa L.

AU - Mitchell, John J.

AU - Mofidi, Shideh

AU - Moseley, Kathryn D.

AU - Mueller, Christine M.

AU - Mulberg, Andrew E.

AU - Nerurkar, Lata S.

AU - Ogata, Beth N.

AU - Pariser, Anne R.

AU - Prasad, Suyash

AU - Pridjian, Gabriella

AU - Rasmussen, Sonja A.

AU - Reddy, Uma M.

AU - Rohr, Frances J.

AU - Singh, Rani H.

AU - Sirrs, Sandra M.

AU - Stremer, Stephanie E.

AU - Tagle, Danilo A.

AU - Thompson, Susan M.

AU - Urv, Tiina K.

AU - Utz, Jeanine R.

AU - van Spronsen, Francjan

AU - Vockley, Jerry

AU - Waisbren, Susan E.

AU - Weglicki, Linda S.

AU - White, Desirée A.

AU - Whitley, Chester B.

AU - Wilfond, Benjamin S.

AU - Yannicelli, Steven

AU - Young, Justin M.

PY - 2014/1/1

Y1 - 2014/1/1

N2 - 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 360. μmol/L before and during pregnancy. The dietary management treatment goal for individuals with PKU is a blood Phe concentration between 120 and 360. μmol/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.

AB - 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 360. μmol/L before and during pregnancy. The dietary management treatment goal for individuals with PKU is a blood Phe concentration between 120 and 360. μmol/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.

KW - Glycomacropeptide

KW - Hyperphenylalaninemia

KW - Large neutral amino acids

KW - Maternal PKU

KW - Phenylketonuria

KW - Sapropterin

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