phenylketonurias

Summary

Summary: A group of autosomal recessive disorders marked by a deficiency of the hepatic enzyme PHENYLALANINE HYDROXYLASE or less frequently by reduced activity of DIHYDROPTERIDINE REDUCTASE (i.e., atypical phenylketonuria). Classical phenylketonuria is caused by a severe deficiency of phenylalanine hydroxylase and presents in infancy with developmental delay; SEIZURES; skin HYPOPIGMENTATION; ECZEMA; and demyelination in the central nervous system. (From Adams et al., Principles of Neurology, 6th ed, p952).

Top Publications

  1. ncbi Phenylketonuria
    Nenad Blau
    Division of Clinical Chemistry and Biochemistry, University Children s Hospital, Zurich, Switzerland
    Lancet 376:1417-27. 2010
  2. ncbi Diagnosis, classification, and genetics of phenylketonuria and tetrahydrobiopterin (BH4) deficiencies
    Nenad Blau
    University Children s Hospital, Zurich, Switzerland
    Mol Genet Metab 104:S2-9. 2011
  3. ncbi Do adult patients with phenylketonuria improve their quality of life after introduction/resumption of a phenylalanine-restricted diet?
    R Gassió
    PKU Follow up Unit, Department of Neurology, Hospital Sant Joan de Deu, Universitat de Barcelona, Spain
    Acta Paediatr 92:1474-8. 2003
  4. ncbi Psychosocial aspects of PKU: hidden disabilities--a review
    J K Gentile
    Medical Coping Clinic, Department of Psychiatry, 11S Medical Intensive Care Unit, Children s Hospital, Boston, MA 02115, USA
    Mol Genet Metab 99:S64-7. 2010
  5. ncbi Living with phenylketonuria: perspectives of patients and their families
    C Bilginsoy
    Department of Economics, University of Utah, Salt Lake City, Utah 84112, USA
    J Inherit Metab Dis 28:639-49. 2005
  6. pmc Consequences of variations in genes that affect dopamine in prefrontal cortex
    Adele Diamond
    Department of Psychiatry, University of British Columbia, BC Children s Hospital, Vancouver, Canada
    Cereb Cortex 17:i161-70. 2007
  7. ncbi Suboptimal outcomes in patients with PKU treated early with diet alone: revisiting the evidence
    G M Enns
    Division of Medical Genetics, Department of Pediatrics, Lucile Packard Children s Hospital, Stanford University, Stanford, CA 94305 5208, USA
    Mol Genet Metab 101:99-109. 2010
  8. pmc Identification of pharmacological chaperones as potential therapeutic agents to treat phenylketonuria
    Angel L Pey
    Department of Biomedicine, University of Bergen, Bergen, Norway
    J Clin Invest 118:2858-67. 2008
  9. ncbi Sustained attention and inhibition of cognitive interference in treated phenylketonuria: associations with concurrent and lifetime phenylalanine concentrations
    S C J Huijbregts
    Department of Clinical Neuropsychology, Vrije Universiteit Amsterdam, Van der Boechorststraat 1, 1081 BT, Amsterdam, The Netherlands
    Neuropsychologia 40:7-15. 2002
  10. ncbi Birth prevalence rates of newborn screening disorders in relation to screening practices in the United States
    Vicki S Hertzberg
    Emory University, Rollins School of Public Health, Department of Biostatistics, Atlanta, GA, USA
    J Pediatr 159:555-60. 2011

Detail Information

Publications300 found, 100 shown here

  1. ncbi Phenylketonuria
    Nenad Blau
    Division of Clinical Chemistry and Biochemistry, University Children s Hospital, Zurich, Switzerland
    Lancet 376:1417-27. 2010
    ..Possible future treatments include enzyme substitution with phenylalanine ammonia lyase, which degrades phenylalanine, and gene therapy to restore phenylalanine hydroxylase activity...
  2. ncbi Diagnosis, classification, and genetics of phenylketonuria and tetrahydrobiopterin (BH4) deficiencies
    Nenad Blau
    University Children s Hospital, Zurich, Switzerland
    Mol Genet Metab 104:S2-9. 2011
    ..The rate of Phe metabolic disposal after Phe challenge may be an additional useful tool in the interpretation of phenotype-genotype correlation...
  3. ncbi Do adult patients with phenylketonuria improve their quality of life after introduction/resumption of a phenylalanine-restricted diet?
    R Gassió
    PKU Follow up Unit, Department of Neurology, Hospital Sant Joan de Deu, Universitat de Barcelona, Spain
    Acta Paediatr 92:1474-8. 2003
    ..To evaluate the possible influence of dietary treatment on the quality of life of adult patients with PKU (phenylketonuria) following late introduction or resumption of a Phe-restricted diet...
  4. ncbi Psychosocial aspects of PKU: hidden disabilities--a review
    J K Gentile
    Medical Coping Clinic, Department of Psychiatry, 11S Medical Intensive Care Unit, Children s Hospital, Boston, MA 02115, USA
    Mol Genet Metab 99:S64-7. 2010
    ..PKU is a disorder in which a less than optimal psychosocial outcome arises from the cumulative impact of relatively mild symptoms. The key to reducing risks associated with PKU is metabolic control throughout life...
  5. ncbi Living with phenylketonuria: perspectives of patients and their families
    C Bilginsoy
    Department of Economics, University of Utah, Salt Lake City, Utah 84112, USA
    J Inherit Metab Dis 28:639-49. 2005
    ....
  6. pmc Consequences of variations in genes that affect dopamine in prefrontal cortex
    Adele Diamond
    Department of Psychiatry, University of British Columbia, BC Children s Hospital, Vancouver, Canada
    Cereb Cortex 17:i161-70. 2007
    ..These sound quite disparate but they all grew systematically out the base laid down by Patricia Goldman-Rakic...
  7. ncbi Suboptimal outcomes in patients with PKU treated early with diet alone: revisiting the evidence
    G M Enns
    Division of Medical Genetics, Department of Pediatrics, Lucile Packard Children s Hospital, Stanford University, Stanford, CA 94305 5208, USA
    Mol Genet Metab 101:99-109. 2010
    ....
  8. pmc Identification of pharmacological chaperones as potential therapeutic agents to treat phenylketonuria
    Angel L Pey
    Department of Biomedicine, University of Bergen, Bergen, Norway
    J Clin Invest 118:2858-67. 2008
    ..Furthermore, PAH activity in mouse liver increased after a 12-day oral administration of low doses of compounds III and IV. Thus, we have identified 2 small molecules that may represent promising alternatives in the treatment of PKU...
  9. ncbi Sustained attention and inhibition of cognitive interference in treated phenylketonuria: associations with concurrent and lifetime phenylalanine concentrations
    S C J Huijbregts
    Department of Clinical Neuropsychology, Vrije Universiteit Amsterdam, Van der Boechorststraat 1, 1081 BT, Amsterdam, The Netherlands
    Neuropsychologia 40:7-15. 2002
    ..We suggest that phe levels should be maintained under 360 micromol/l until approximately age 12, when development of attentional control approaches an adult level...
  10. ncbi Birth prevalence rates of newborn screening disorders in relation to screening practices in the United States
    Vicki S Hertzberg
    Emory University, Rollins School of Public Health, Department of Biostatistics, Atlanta, GA, USA
    J Pediatr 159:555-60. 2011
    ....
  11. ncbi Structural basis of autoregulation of phenylalanine hydroxylase
    B Kobe
    St Vincent s Institute of Medical Research, Fitzroy, Victoria, Australia
    Nat Struct Biol 6:442-8. 1999
    ....
  12. ncbi Phenylalanine tolerance can already reliably be assessed at the age of 2 years in patients with PKU
    F J van Spronsen
    Department of Pediatrics, Beatrix Children s Hospital, and Center for Liver, Digestive and Metabolic Diseases, University Medical Center of Groningen, University of Groningen, Groningen, The Netherlands
    J Inherit Metab Dis 32:27-31. 2009
    ..So far, little is known about the course of Phe tolerance or the ability of both pre-treatment Phe and Phe tolerance at early age to predict Phe tolerance at later age...
  13. ncbi Tetrahydrobiopterin (BH4) in PKU: effect on dietary treatment, metabolic control, and quality of life
    B Ziesch
    University Hospital for Children and Adolescents, University of Leipzig, Leipzig, Germany
    J Inherit Metab Dis 35:983-92. 2012
    ..Tetrahydrobiopterin (BH(4))-sensitive phenylketonuria (PKU) can be treated with sapropterin dihydrochloride. We studied metabolic control and health-related quality of life (HRQoL) in PKU patients treated with BH(4)...
  14. pmc Nutritional treatment for inborn errors of metabolism: indications, regulations, and availability of medical foods and dietary supplements using phenylketonuria as an example
    Kathryn M Camp
    Office of Dietary Supplements, National Institutes of Health, Bethesda, MD 20892, USA
    Mol Genet Metab 107:3-9. 2012
    ..Throughout the paper, we use the nutritional treatment of phenylketonuria as an example of IEM treatment...
  15. ncbi Living with phenylketonuria from the point of view of children, adolescents, and young adults: a qualitative study
    Vincenzo Di Ciommo
    Unit of Epidemiology, Department of Medical Directorate, Bambino Gesu Children s Hospital, Rome, Italy
    J Dev Behav Pediatr 33:229-35. 2012
    ....
  16. ncbi Inhibitory control in children with phenylketonuria
    Shawn E Christ
    Department of Psychological Sciences, University of Missouri Columbia, Department of Psychology, Washington University, St Louis, MO 65211, USA
    Dev Neuropsychol 30:845-64. 2006
    ..Findings suggest that the inhibitory deficit associated with PKU is subtle and that inconsistent findings in past studies may be largely due to the insensitivity of experimental manipulations in some tasks...
  17. ncbi Quality of life and psychologic adjustment in children and adolescents with early treated phenylketonuria can be normal
    Markus A Landolt
    Division of Psychosomatics and Psychiatry, University Children s Hospital, Zurich, Switzerland
    J Pediatr 140:516-21. 2002
    ..To assess quality of life and psychologic adjustment in children and adolescents with early treated phenylketonuria (PKU)...
  18. ncbi Novel pharmacological chaperones that correct phenylketonuria in mice
    Sandra Santos-Sierra
    Sections of Biochemical and Clinical Pharmacology, Department of Medical Genetics, Molecular and Clinical Pharmacology, Innsbruck Medical University, 6020 Innsbruck, Austria
    Hum Mol Genet 21:1877-87. 2012
    ..Notably, benzylhydantoin was twice as effective as tetrahydrobiopterin. In conclusion, we identified two PCs with high in vivo efficacy that may be further developed into a more effective drug treatment of PKU...
  19. ncbi Outcomes beyond phenylalanine: an international perspective
    Francois Feillet
    Reference Centre for Inborn Errors of Metabolism, Inserm U954, Department of Pediatrics, Children s Hospital of Nancy, Allee du Morvan, Vandoeuvre les Nancy 54500, France
    Mol Genet Metab 99:S79-85. 2010
    ..The objective is to emphasize that management of PKU goes well beyond addressing the biochemical nature of this disease in order to achieve optimal patient outcomes...
  20. pmc Using change in plasma phenylalanine concentrations and ability to liberalize diet to classify responsiveness to tetrahydrobiopterin therapy in patients with phenylketonuria
    Rani H Singh
    Department of Human Genetics, Emory University School of Medicine, Decatur, GA 30033, USA
    Mol Genet Metab 104:485-91. 2011
    ..Diet liberalization is an essential component of BH(4)-responsiveness classification...
  21. pmc Parenting a child with phenylketonuria or galactosemia: implications for health-related quality of life
    Amber E Ten Hoedt
    Department of Pediatrics H7 270, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
    J Inherit Metab Dis 34:391-8. 2011
    ..The insight that emotional support and loss of friendship influence the HRQoL of the parents enables treating physicians to provide better support for these parents...
  22. ncbi Neuropsychological outcome of subjects participating in the PKU adult collaborative study: a preliminary review
    V L Brumm
    CHLA Division of Neurology, Keck School of Medicine, University of Southern California, 4650 Sunset Blvd, MS 82, Los Angeles, CA 90027, USA
    J Inherit Metab Dis 27:549-66. 2004
    ..Future longitudinal investigation with a larger sample size will assist in clarifying the aetiology of neuropsychological deficits and association with treatment history...
  23. ncbi Adherence to diet and quality of life in patients with phenylketonuria
    G Cotugno
    Division of Metabolic Diseases, Bambino Gesu Children s Hospital, Rome, Italy
    Acta Paediatr 100:1144-9. 2011
    ..To investigate adherence to dietary treatment and quality of life (QoL) in patients with phenylketonuria (PKU)...
  24. ncbi Mechanisms underlying responsiveness to tetrahydrobiopterin in mild phenylketonuria mutations
    Angel L Pey
    Centro de Biologia Molecular Severo Ochoa, CSIC Universidad Autonoma de Madrid, Madrid, Spain
    Hum Mutat 24:388-99. 2004
    ..Both effects of BH4 on PAH, i.e., the chemical chaperone effect preventing protein misfolding and the protection from inactivation, may be relevant mechanisms of the responsive phenotype...
  25. ncbi Modulation of the activity of newly synthesized human phenylalanine hydroxylase mutant proteins by low-molecular-weight compounds
    Cátia Nascimento
    Metabolism and Genetics Group, iMed UL, Faculdade Farmácia da Universidade de Lisboa, Av Prof Gama Pinto, 1649 003 Lisbon, Portugal
    Protein J 27:392-400. 2008
    ..Coli molecular chaperones we postulate that glycerol and TMAO rescue results from a direct stabilizing effect of the newly synthesized mutant hPAH enzymes...
  26. ncbi Behaviour and school achievement in patients with early and continuously treated phenylketonuria
    B A Stemerdink
    Department of Developmental, State University Groningen, The Netherlands
    J Inherit Metab Dis 23:548-62. 2000
    ..More specifically, school achievement as well as social and task-oriented behaviour (at home..
  27. ncbi The behavioral profile of severe mental retardation in a genetic mouse model of phenylketonuria
    Simona Cabib
    Dipartimento di Psicologia, Universita La Sapienza, Via dei Marsi 78, Rome 1 00195, Italy
    Behav Genet 33:301-10. 2003
    ..These results indicate that Pah(enu2) mice show pathological cognitive deficits and support their use to test hypotheses about neurodevelopmental disturbances involved in mental retardation...
  28. ncbi Rationale for the German recommendations for phenylalanine level control in phenylketonuria 1997
    P Burgard
    Fachrichtung Psychologie, Universitat des Saarlandes, Im Stadtwald, Saarbrucken, Germany
    Eur J Pediatr 158:46-54. 1999
    ....
  29. pmc Improved nutritional management of phenylketonuria by using a diet containing glycomacropeptide compared with amino acids
    Sandra C van Calcar
    Waisman Center, University of Wisconsin, Madison, WI 53706, USA
    Am J Clin Nutr 89:1068-77. 2009
    ..Glycomacropeptide (GMP), an intact protein formed during cheese production, contains minimal phenylalanine...
  30. ncbi Phenylalanine hydroxylase deficiency
    John J Mitchell
    Department of Medical Genetics, McGill University Health Center, Montreal, Canada
    Genet Med 13:697-707. 2011
    ..Molecular genetic testing of the phenylalanine hydroxylase gene is available for genetic counseling purposes to determine carrier status of at-risk relatives and for prenatal testing...
  31. pmc Purification and use of glycomacropeptide for nutritional management of phenylketonuria
    Caitlin E Laclair
    Dept of Food Science, Univ of Wisconsin, Madison, WI 53706, USA
    J Food Sci 74:E199-206. 2009
    ..Nutritionally complete GMP foods created with high purity GMP provide individuals with PKU with more options to manage PKU, which may lead to improved compliance and quality of life...
  32. pmc Evaluation of orally administered PEGylated phenylalanine ammonia lyase in mice for the treatment of Phenylketonuria
    Christineh N Sarkissian
    Departments of Biology, Human Genetics and Pediatrics, McGill University, and Debelle Laboratory, McGill University Montreal Children s Hospital Research Institute, 2300 Tupper Street, A 717, Montreal, QC, H3H 1P3 Canada
    Mol Genet Metab 104:249-54. 2011
    ....
  33. ncbi Structure of tetrameric human phenylalanine hydroxylase and its implications for phenylketonuria
    F Fusetti
    Department of Chemistry, University of California and Physical Biosciences Division, Lawrence Berkeley National Laboratory, Berkeley, California 94720, USA
    J Biol Chem 273:16962-7. 1998
    ..Their effects on the structural and cellular stability of the enzyme are discussed...
  34. pmc Pathologic and immunohistochemical findings in hypothalamic and mesencephalic regions in the pah(enu2) mouse model for phenylketonuria
    Jennifer E Embury
    Department of Biochemistry and Molecular Biology, College of Medicine, University of Florida, Gainesville, Florida 32610, USA
    Pediatr Res 58:283-7. 2005
    ..The CD11b-positive cells and increased inducible nitric oxide synthase expression in these regions may function in a neuroregulatory manner to compensate for alterations in dopamine metabolism...
  35. ncbi Phenylalanine blood levels and clinical outcomes in phenylketonuria: a systematic literature review and meta-analysis
    Susan E Waisbren
    Children s Hospital Boston, 1 Autumn Street, Room 525, Boston, MA 02115, USA
    Mol Genet Metab 92:63-70. 2007
    ..In conclusion, these results confirm a significant correlation between blood Phe level and IQ in patients with PKU, and support the use of Phe as a predictive biomarker for IQ in clinical trials...
  36. ncbi Motor function under lower and higher controlled processing demands in early and continuously treated phenylketonuria
    S C J Huijbregts
    Department of Clinical Neuropsychology, Vrije Universiteit Amsterdam, The Netherlands
    Neuropsychology 17:369-79. 2003
    ..Correlations with historical phenylalanine levels indicated a later maturation of the level of control required by the pursuit task compared with the tracking task...
  37. ncbi Characterization of white matter alterations in phenylketonuria by magnetic resonance relaxometry and diffusion tensor imaging
    Peter Vermathen
    Department Clinical Research, Unit for MR Spectroscopy and Methodology, University Berne, Bern, Switzerland
    Magn Reson Med 58:1145-56. 2007
    ..Intramyelinic edema combined with vacuolization is a likely cause of the WM alterations. Correlations between diffusivity and Phe concentrations confirm vulnerability of WM to high Phe concentrations...
  38. ncbi Twenty-five years of research on neurocognitive outcomes in early-treated phenylketonuria: intelligence and executive function
    Kathryn DeRoche
    Department of Applied Statistics and Research Methods, University of Northern Colorado, Greeley, CO 80639, USA
    Dev Neuropsychol 33:474-504. 2008
    ..The results are discussed in terms of the contributions this meta-analysis makes to our understanding of neurocognitive outcomes in early-treated PKU, as well as suggestions for the conduct and reporting of future research in this area...
  39. ncbi Neuropsychological speed tests and blood phenylalanine levels in patients with phenylketonuria: a meta-analysis
    Julia Albrecht
    Centre for Paediatric and Adolescent Medicine, University of Heidelberg, Im Neuenheimer Feld 430, D 69120 Heidelberg, Germany
    Neurosci Biobehav Rev 33:414-21. 2009
    ..The same effect size is predicted for adult phenylalanine concentrations between 750 and 1500mumol/L not suggesting a preference for any of the published treatment recommendations for adulthood...
  40. ncbi Management of phenylketonuria in Europe: survey results from 19 countries
    Nenad Blau
    University Children s Hospital, Zurich, Switzerland
    Mol Genet Metab 99:109-15. 2010
    ..There is an urgent need to pool long-term data in PKU registries in order to generate an evidence-based international guideline...
  41. ncbi Development of intelligence in early treated phenylketonuria
    P Burgard
    Department of General Paediatrics, University of Heidelberg, Germany
    Eur J Pediatr 159:S74-9. 2000
    ..For historical reasons there is no research on IQ development of early treated patients in middle or late adulthood, and it remains unclear whether older age groups might carry new risks...
  42. ncbi Phenylketonuria in adulthood: a collaborative study
    R Koch
    Children s Hospital Los Angeles, Department of Pediatrics, Keck School of Medicine, University of Southern California, 90027, USA
    J Inherit Metab Dis 25:333-46. 2002
    ..Early dietary discontinuation for subjects with PKU is associated with poorer outcomes not only in intellectual ability, but also in achievement test scores and increased rates of medical and behavioural problems...
  43. pmc Predicted effects of missense mutations on native-state stability account for phenotypic outcome in phenylketonuria, a paradigm of misfolding diseases
    Angel L Pey
    Department of Biomedicine, University of Bergen, Bergen, Norway
    Am J Hum Genet 81:1006-24. 2007
    ..However, additional factors must be considered that may contribute to the patient phenotype, such as possible effects on catalysis and interindividual differences in physiological and metabolic processes...
  44. pmc Evaluation of quality of life and description of the sociodemographic state in adolescent and young adult patients with phenylketonuria (PKU)
    Eva Simon
    Department of General Pediatrics, Heinrich Heine University, Duesseldorf, Germany
    Health Qual Life Outcomes 6:25. 2008
    ..Aim of the study was to analyse quality of life and social status, which are important parameters for an overall estimation of success of treatment apart from intellectual outcome in adult PKU patients...
  45. ncbi Phenylketonuria: High plasma phenylalanine decreases cerebral protein synthesis
    Marieke Hoeksma
    Beatrix Children s Hospital, University Medical Center Groningen, University of Groningen, Section of Metabolic Diseases, P O Box 30 001, 9700 RB Groningen, The Netherlands
    Mol Genet Metab 96:177-82. 2009
    ..Hence, we speculate that it is important to continue dietary treatment into adulthood, aiming at plasma phenylalanine concentrations <600-800micromol/l...
  46. pmc Large neutral amino acids block phenylalanine transport into brain tissue in patients with phenylketonuria
    J Pietz
    Department of Pediatric Neurology, University of Heidelberg, D 69120 Heidelberg, Germany
    J Clin Invest 103:1169-78. 1999
    ....
  47. pmc Randomised controlled trial of tyrosine supplementation on neuropsychological performance in phenylketonuria
    M L Smith
    Department of Psychology, University of Toronto, Mississauga, Ontario, Canada
    Arch Dis Child 78:116-21. 1998
    ..To test the efficacy of tyrosine supplementation, as an adjunct to dietary treatment, on neuropsychological test performance in individuals with phenylketonuria...
  48. pmc Loss of function in phenylketonuria is caused by impaired molecular motions and conformational instability
    Søren W Gersting
    Department of Molecular Pediatrics, Children s Research Center, Dr von Hauner Children s Hospital, Ludwig Maximilians University, 80337 Munich, Germany
    Am J Hum Genet 83:5-17. 2008
    ..Thus, PKU has evolved from a model of a genetic disease that leads to severe neurological impairment to a model of a treatable protein-folding disease with loss of function...
  49. pmc Correction of kinetic and stability defects by tetrahydrobiopterin in phenylketonuria patients with certain phenylalanine hydroxylase mutations
    Heidi Erlandsen
    Department of Molecular Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA
    Proc Natl Acad Sci U S A 101:16903-8. 2004
    ..Of fundamental importance is the observation that BH4 appears to increase Phe catabolism if at least one of the two heterozygous mutations has any residual activity remaining...
  50. ncbi The reality of dietary compliance in the management of phenylketonuria
    Anita MacDonald
    Birmingham Children s Hospital, Steelhouse Lane, Birmingham B4 6NH, UK
    J Inherit Metab Dis 33:665-70. 2010
    ....
  51. ncbi Meta-analysis of neuropsychological symptoms of adolescents and adults with PKU
    J J Moyle
    School of Psychology, The University of Western Australia, Perth, Australia
    Neuropsychol Rev 17:91-101. 2007
    ..Future research utilizing an integrative approach and detailed analysis of specific cognitive domains will assist both the scientist and clinician, and ultimately the patient...
  52. ncbi Phenylketonuria as a protein misfolding disease: The mutation pG46S in phenylalanine hydroxylase promotes self-association and fibril formation
    João Leandro
    Department of Biomedicine, University of Bergen, Jonas Lies vei 91, N 5009 Bergen, Norway
    Biochim Biophys Acta 1812:106-20. 2011
    ....
  53. ncbi Remarkable differences: the course of life of young adults with galactosaemia and PKU
    A M Bosch
    Department of Pediatrics, Academic Medical Center, University of Amsterdam, G8205, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands
    J Inherit Metab Dis 32:706-12. 2009
    ..We conclude that it is essential that parents and clinicians encourage children with galactosaemia to participate in peer-related activities in order to stimulate social performance, which may result in a more normal CoL...
  54. ncbi Executive functioning and speed of processing in phenylketonuria
    Shelley Channon
    Department of Psychology, University College London, and Department of Metabolic Medicine, National Hospital for Neurology and Neurosurgery, University College London Hospitals, United Kingdom
    Neuropsychology 19:679-86. 2005
    ..A cognitive slowing account may prove more informative in adults with PKU, but more evidence is needed. The findings suggest that continuous dietary management is a fairly successful strategy in terms of cognitive outcome for adults...
  55. ncbi The truth of treating patients with phenylketonuria after childhood: the need for a new guideline
    F J van Spronsen
    Section of Metabolic Diseases, Beatrix Children s Hospital, University Medical Centre of Groningen, PO Box 30 001, 9700 RB, Groningen, The Netherlands
    J Inherit Metab Dis 31:673-9. 2008
    ..In addition, guidelines must address not only what has to be done but also how it can be done, thereby improving concordance with the recommendations for treatment and management...
  56. ncbi The course of life and quality of life of early and continuously treated Dutch patients with phenylketonuria
    A M Bosch
    Department of Pediatrics, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
    J Inherit Metab Dis 30:29-34. 2007
    ..The results of this study demonstrate that although PKU is a chronic disease with the burden of strict dietary control, early and continuously treated patients with PKU can have a normal health-related quality of life and course of life...
  57. ncbi Executive functioning, memory, and learning in phenylketonuria
    Shelley Channon
    Department of Psychology, University College London, London, England
    Neuropsychology 18:613-20. 2004
    ..Nor did they differ significantly on recall or recognition memory. Overall, the findings provided little support for the executive deficit hypothesis. A possible explanation in terms of slowed information processing speed is explored...
  58. ncbi Effect of fish oil supplementation on fatty acid status, coordination, and fine motor skills in children with phenylketonuria
    Skadi Beblo
    Division of Metabolic Diseases and Nutrition, Dr von Haunersches Kinderspital, Ludwig Maximilians University, Munich, Germany
    J Pediatr 150:479-84. 2007
    ..To investigate effects of long-chain omega-3 polyunsaturated fatty acids (LC-PUFA) on motor skills in patients with phenylketonuria (PKU)...
  59. ncbi Fish oil supplementation improves visual evoked potentials in children with phenylketonuria
    S Beblo
    Division of Metabolic Diseases and Nutrition, Dr. von Haunersches Kinderspital, Munich, Germany
    Neurology 57:1488-91. 2001
    ..The authors conclude that omega-3 LC-PUFA are essential substrates for nervous system function even beyond infancy...
  60. ncbi Double blind placebo control trial of large neutral amino acids in treatment of PKU: effect on blood phenylalanine
    R Matalon
    Department of Pediatrics, University of Texas Medical Branch, Children s Hospital, Galveston, Texas, USA
    J Inherit Metab Dis 30:153-8. 2007
    ..Long-term studies will be needed to validate the acceptability, efficacy and safety of such treatment...
  61. ncbi Impaired glutamatergic synaptic transmission in the PKU brain
    A E Martynyuk
    Department of Anesthesiology, University of Florida, Gainesville, FL, USA
    Mol Genet Metab 86:S34-42. 2005
    ....
  62. ncbi Monogenic traits are not simple: lessons from phenylketonuria
    C R Scriver
    DeBelle Laboratory for Biochemical Genetics, Montreal Children s Hospital, 2300 Tupper Street, Montreal, Quebec, Canada H3H 1P3
    Trends Genet 15:267-72. 1999
    ....
  63. ncbi Does dietary DHA improve neural function in children? Observations in phenylketonuria
    Berthold Koletzko
    Division of Metabolic Diseases and Nutritional Medicine, Dr von Hauner Children s Hospital, University of Munich Medical Centre, Lindwurmstr 4, 80337 Munich, Germany
    Prostaglandins Leukot Essent Fatty Acids 81:159-64. 2009
    ..Since PKU children are generally healthy and have normal energy and fatty acid metabolism, these data lead us to conclude that childhood populations in general require preformed n-3 LC-PUFA to achieve optimal neurological function...
  64. ncbi Executive function in early-treated phenylketonuria: profile and underlying mechanisms
    Shawn E Christ
    Department of Psychological Sciences, 210 McAlester Hall, University of Missouri, Columbia, MO 65203, USA
    Mol Genet Metab 99:S22-32. 2010
    ..In closing, this review identifies remaining unanswered questions and future avenues for research...
  65. ncbi Effects of phenylalanine on the survival and neurite outgrowth of rat cortical neurons in primary cultures: possible involvement of brain-derived neurotrophic factor
    Duan Li
    Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Institute for Pediatric Research, 1665 Kong Jiang Rd, Shanghai 200092, China
    Mol Cell Biochem 339:1-7. 2010
    ..Considering the important role of BDNF in normal brain development and function, these L: -Phe-induced changes in BDNF in PKU brain may be a critical element of the neurological symptoms of PKU...
  66. ncbi Behavioural effects of phenylalanine-free amino acid tablet supplementation in intellectually disabled adults with untreated phenylketonuria
    H Serap Kalkanoglu
    Department of Paediatrics, Nutrition and Metabolism Unit, Hacettepe University, Ankara, Turkey
    Acta Paediatr 94:1218-22. 2005
    ..To evaluate the effects of phenylalanine (Phe)-free essential amino acid (AA) tablets enriched in tyrosine and tryptophan on the performance of intellectually disabled adult patients with untreated phenylketonuria (PKU)...
  67. ncbi Phenylketonuria: a 21st century perspective
    Francjan J van Spronsen
    Beatrix Children s Hospital, University Medical Center of Groningen, PO Box 30 001, 9700 RB Groningen, The Netherlands
    Nat Rev Endocrinol 6:509-14. 2010
    ..This Review provides an overview of the history of phenylketonuria, the challenges of treatment today and the treatment possibilities in the near future...
  68. ncbi Phenylalanine-restricted diet should be life long. A case report on long-term follow-up of an adolescent with untreated phenylketonuria
    Joav Merrick
    National Institute of Child Health and Human Development, Division of Community Health, Department of Family Medicine, Ben Gurion University, Beer Sheva, Israel
    Int J Adolesc Med Health 15:165-8. 2003
    ..In general, this patient's quality of life had increased. We therefore recommend life-long treatment with phenylalanine restricted diet for persons with previously treated, and also for those with untreated, phenylketonuria...
  69. ncbi Biochemical markers associated with executive function in adolescents with early and continuously treated phenylketonuria
    R Sharman
    Institute of Health and Biomedical Innovation, Queensland University of Technology, Queensland, Australia
    Clin Genet 75:169-74. 2009
    ..Correlations between EF and biochemistry in children with PKU showed that participant's lifetime phe : tyr ratio was positively and significantly associated with EF impairment, more so than phe-only measures...
  70. ncbi Quality of life in noncompliant adults with phenylketonuria after resumption of the diet
    M Bik-Multanowski
    Chair of Pediatrics, Jagiellonian University, ul Wielicka 265, 30 663, Krakow, Poland
    J Inherit Metab Dis 31:S415-8. 2008
    ..The aim of our study was to assess the change in quality of life in adult patients returning to the diet and to define the reasons for failure in diet resumption...
  71. ncbi Phenylketonuria: dietary and therapeutic challenges
    M Giovannini
    Department of Pediatrics, San Paolo Hospital, University of Milan, Milan, Italy
    J Inherit Metab Dis 30:145-52. 2007
    ..New strategies--such as supply of tetrahydrobiopterin--need to be optimized in terms of targets, patients and expected outcomes...
  72. ncbi Situational analysis of dietary challenges of the treatment regimen for children and adolescents with phenylketonuria and their primary caregivers
    Carolyn E Ievers-Landis
    Division of Behavioral Pediatrics and Psychology, Department of Pediatrics, Rainbow Babies and Children s Hospital, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106 6038, USA
    J Dev Behav Pediatr 26:186-93. 2005
    ..05)...
  73. ncbi A study of gene expression profiles of cultured embryonic rat neurons induced by phenylalanine
    Huiwen Zhang
    Department of Endocrinology and Genetic Metabolism, Xin Hua Hospital, Shanghai Institute for Pediatric Research, Shanghai Second Medical University, Shanghai 200092, People s Republic of China
    Metab Brain Dis 20:61-72. 2005
    ..Our study also suggests that the excitatory neurotransmitter glutamate may play a role in the neural pathology of PKU...
  74. ncbi Long-term follow-up study of patients with phenylketonuria detected by the newborn screening programme in Japan
    K Aoki
    Department of Research Development, Aiiku Maternal and Child Health Center, 5 6 8 Minami, Minato ku, Tokyo, 106 8580, Japan
    J Inherit Metab Dis 30:608. 2007
    ..Further, the evaluations of the effectiveness of the two initiatives as well as the treatment guidelines issued should be based on outcome data, which depend on the continuation of the follow-up study of patients with PKU...
  75. ncbi Diet in phenylketonuria: a snapshot of special dietary costs and reimbursement systems in 10 international centers
    A Belanger-Quintana
    Unidad de Enfermedades Metabolicas, Servicio de Pediatria, Hospital Ramon y Cajal, Madrid, Spain
    Mol Genet Metab 105:390-4. 2012
    ..To gather exploratory data on the costs and reimbursement of special dietary foods used in the management of phenylketonuria (PKU) from ten international specialist PKU centers...
  76. ncbi Reduced cerebral fluoro-L-dopamine uptake in adult patients suffering from phenylketonuria
    Christian Landvogt
    Department of Nuclear Medicine, University of Mainz, Mainz, Germany
    J Cereb Blood Flow Metab 28:824-31. 2008
    ..The linear graphical analysis shows reduced k3S in striatum, indicating reduced DOPA decarboxylase activity...
  77. ncbi Does maternal knowledge impact blood phenylalanine concentration in Turkish children with phenylketonuria?
    H Gokmen Ozel
    Faculty of Health Sciences, Department of Nutrition and Dietetics, Hacettepe University, 06100, Ankara, Turkey
    J Inherit Metab Dis 31:S213-7. 2008
    ..We would like to implement an easier method of measuring Phe exchanges to improve dietary knowledge in the mothers...
  78. pmc "MY PKU": increasing self-management in patients with phenylketonuria. A randomized controlled trial
    Amber E Ten Hoedt
    Department of Pediatrics, Academic Medical Center AMC, University of Amsterdam, AZ Amsterdam, The Netherlands
    Orphanet J Rare Dis 6:48. 2011
    ..We aimed to assess whether increased self-management of PKU patients and/or their parents is feasible and safe, by providing direct online access to blood Phe values without immediate professional guidance...
  79. ncbi PKU: high plasma phenylalanine concentrations are associated with increased prevalence of mood swings
    Karen Anjema
    Beatrix Children s Hospital, University Medical Centre Groningen, University of Groningen, Section of Metabolic Diseases, The Netherlands
    Mol Genet Metab 104:231-4. 2011
    ..The interviewer as well as the respondents were blinded with regard to the phenylalanine concentration...
  80. ncbi Rapid screening of phenylketonuria using a CD microfluidic device
    Bin Chen
    Department of Laboratory Medicine, Guangzhou First Municipal People s Hospital, Affiliated to Guangzhou Medical College, Guangzhou, Guangdong 510180, China
    J Chromatogr A 1218:1907-12. 2011
    ..Results of the hybridization assay were confirmed by DNA sequencing. This CD-chip based hybridization assay features short analysis time, simple operation and low cost, thus has the potential to serve as the tool for PKU screening...
  81. ncbi Blood phenylalanine control in phenylketonuria: a survey of 10 European centres
    K Ahring
    Department of PKU, Kennedy Centre, Glostrup, Denmark
    Eur J Clin Nutr 65:275-8. 2011
    ..Only limited data are available on the blood phenylalanine (Phe) concentrations achieved in European patients with phenylketonuria (PKU) on a low-Phe diet...
  82. pmc Introduction of sapropterin dihydrochloride as standard of care in patients with phenylketonuria
    H J Vernon
    McKusick Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
    Mol Genet Metab 100:229-33. 2010
    ..Even in patients who were not considered to be responders, the introduction of sapropterin provided a tool to reconnect with patients and re-introduce beneficial dietary measures...
  83. ncbi Follow up of phenylketonuria patients
    M Demirkol
    Div Nutrition and Metabolism, Children s Hospital, Istanbul Medical Faculty, Istanbul University, Istanbul, Turkey
    Mol Genet Metab 104:S31-9. 2011
    ....
  84. pmc Bone impairment in phenylketonuria is characterized by circulating osteoclast precursors and activated T cell increase
    Ilaria Roato
    Center for Experimental Research and Medical Studies, A O U San Giovanni Battista, Torino, Italy
    PLoS ONE 5:e14167. 2010
    ..Phenylketonuria (PKU) is a rare inborn error of metabolism often complicated by a progressive bone impairment of uncertain etiology, as documented by both ionizing and non- ionizing techniques...
  85. pmc 5-Hydroxytryptophan during critical postnatal period improves cognitive performances and promotes dendritic spine maturation in genetic mouse model of phenylketonuria
    Diego Andolina
    Dipartimento di Psicologia and Centro Daniel Bovet, Sapienza University, Rome, Italy
    Int J Neuropsychopharmacol 14:479-89. 2011
    ....
  86. pmc PKU is a reversible neurodegenerative process within the nigrostriatum that begins as early as 4 weeks of age in Pah(enu2) mice
    Jennifer E Embury
    Department of Biochemistry and Molecular Biology, PO Box 100245, College of Medicine, University of Florida, Gainesville, FL 32610, USA
    Brain Res 1127:136-50. 2007
    ....
  87. pmc Glycomacropeptide, a low-phenylalanine protein isolated from cheese whey, supports growth and attenuates metabolic stress in the murine model of phenylketonuria
    Patrick Solverson
    Department of Nutritional Sciences, University of Wisconsin Madison, 53706, USA
    Am J Physiol Endocrinol Metab 302:E885-95. 2012
    ..In summary, GMP provides a physiological source of low-phe dietary protein that promotes growth and attenuates the metabolic stress induced by a high-phe casein or low-phe AA diet in PKU mice...
  88. ncbi Is there a relationship between plasma phenylalanine and cholesterol in phenylketonuric patients under dietary treatment?
    C Colomé
    Servei de Bioquimica, Servei de Pediatria i Neuropediatria, Unitat Integrada, Hospital Sant Joan de Déu Hospital Clínic, Universitat de Barcelona, Barcelona, Spain
    Clin Biochem 34:373-6. 2001
    ....
  89. ncbi Future treatment strategies in phenylketonuria
    Francjan J van Spronsen
    Section of Metabolic Diseases, Beatrix Children s Hospital, University Medical Centre of Groningen, PO Box 30 001, 9700 RB, Groningen, The Netherlands
    Mol Genet Metab 99:S90-5. 2010
    ..These therapeutic strategies propose to treat PKU at various levels, including nutritional intake, gut, liver, and blood-brain barrier, and have the potential to further improve outcome in PKU...
  90. ncbi Age-related working memory impairments in children with prefrontal dysfunction associated with phenylketonuria
    Desiree A White
    Department of Psychology, Washington University, St Louis, Missouri 63130, USA
    J Int Neuropsychol Soc 8:1-11. 2002
    ..Instead, deficits were observed only in older children, suggesting the presence of a developmental deficit rather than a developmental delay in the working memory of children with PKU...
  91. ncbi A preliminary report on dopamine system reactivity in PKU: acute effects of haloperidol on neuropsychological, physiological, and neuroendocrine functions
    Monica Luciana
    Department of Psychology, University of Minnesota, 75 East River Road, Minneapolis, MN 55455, USA
    Psychopharmacology (Berl) 175:18-25. 2004
    ..It has been suggested that these deficits are due to disruptions in the mesocortical dopamine system that projects to the prefrontal cortex...
  92. ncbi Protein substitutes for PKU: what's new?
    A MacDonald
    The Children s Hospital, Birmingham, UK
    J Inherit Metab Dis 27:363-71. 2004
    ..These findings are important in rationalizing treatment strategies, improving patient compliance and overall in improving blood phenylalanine control...
  93. ncbi The mechanism of BH4 -responsive hyperphenylalaninemia--as it occurs in the ENU1/2 genetic mouse model
    Christineh N Sarkissian
    Department of Human Genetics, McGill University Montreal Children s Hospital Research Institute, Montreal, Quebec, Canada
    Hum Mutat 33:1464-73. 2012
    ..By boosting blood Phe concentrations, and by BH(4) supplementation, we have revealed novel insights into the processing and regulation of the ENU1/2-mutant PAH...
  94. ncbi Cross-sectional study of bone metabolism with nutrition in adult classical phenylketonuric patients diagnosed by neonatal screening
    Hironori Nagasaka
    Department of Pediatrics, Takarazuka City Hospital, 4 5 1 Kohama Cho, Takarazuka 665 0827, Japan
    J Bone Miner Metab 29:737-43. 2011
    ..001; males, P < 0.01). None of the bone parameters correlated significantly with serum phenylalanine or nutrient intake. PKU patients exhibited lower VD status and more rapid bone resorption despite normal calcium-VD intakes...
  95. ncbi Relationships between lumbar bone mineral density and biochemical parameters in phenylketonuria patients
    Martijn J de Groot
    Beatrix Children s Hospital, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
    Mol Genet Metab 105:566-70. 2012
    ..The etiology of reduced bone mineral density (BMD) in phenylketonuria (PKU) is unknown. Reduced BMD may be inherent to PKU and/or secondary to its dietary treatment...
  96. pmc Nutritional management of PKU with glycomacropeptide from cheese whey
    D M Ney
    Department of Nutritional Sciences, University of Wisconsin, Madison, WI 53706, USA
    J Inherit Metab Dis 32:32-9. 2009
    ..In summary, food products made with GMP that is supplemented with limiting indispensable amino acids provide a palatable alternative source of protein that may improve dietary compliance and metabolic control of PKU...
  97. ncbi A study of bone turnover markers in prepubertal children with phenylketonuria
    Jadwiga Ambroszkiewicz
    Department of Biochemistry, Institute of Mother and Child, ul Kasprzaka 17a, 01 211, Warsaw, Poland
    Eur J Pediatr 163:177-8. 2004
  98. ncbi New approach to osteopenia in phenylketonuric patients
    B Perez-Duenas
    Department of Pediatrics Hospital Sant Joan de Déu Clínic, University of Barcelona, Spain
    Acta Paediatr 91:899-904. 2002
    ..The response to treatment with low-dose 1.25-(OH)2 vitamin D in patients with osteopenia was evaluated...
  99. ncbi "Hypotyrosinemia" in phenylketonuria
    W B Hanley
    Division of Clinical and Biochemical Genetics, The Hospital for Sick Children, Toronto, Ontario, Canada
    Mol Genet Metab 69:286-94. 2000
    ..8 micromol/L in infants, children, and adolescents in the literature review. Our data support the previously undocumented statements in the literature that plasma tyrosine levels are low in PKU...
  100. ncbi How practical are recommendations for dietary control in phenylketonuria?
    J H Walter
    Willink Biochemical Genetic Unit, Royal Manchester Children s Hospital, Manchester M27 4HA, UK
    Lancet 360:55-7. 2002
    ..Our results indicate the difficulty of maintaining control in phenylketonuria, especially in older rather than younger children...
  101. ncbi Visual event-related potentials in children with phenylketonuria
    R M Henderson
    Department of Vision Sciences, Glasgow Caledonian University, Scotland
    Acta Paediatr 89:52-7. 2000
    ..The lack of differences in reaction time and P3 may be due to relatively good Phe control in children with PKU, or to the simplicity of the task. Suggestions are made for future ERP studies of PKU...

Research Grants62

  1. STRUCTURAL UNDERSTANDING OF PHENYLKETONURIA (PKU)
    RAYMOND STEVENS; Fiscal Year: 2004
    ..However it is important to determine the three dimensional structure of the full-length enzyme in order to fully understand the complex regulatory, catalytic, and stability issues associated with this family of enzymes. ..
  2. Genetic Reconstitution for Phenylketonuria
    Savio Woo; Fiscal Year: 2006
    ..abstract_text> ..
  3. Novel therapy for monoamine neurotransmitter deficiency in PKU
    Cary O Harding; Fiscal Year: 2013
    ..Our goal is to thoroughly evaluate these novel therapeutic approaches in Pahenu2 mice and to choose specific interventions for a future clinical trial in humans with PKU. ..
  4. Structural determinants of DTI observations in developing cortex and white matter
    Christopher D Kroenke; Fiscal Year: 2013
    ..We will also use this experimental strategy to expand the capabilities of MRI to studies of earlier stages of brain development. ..
  5. Mechanisms of Neurotransmitter Biosynthesis
    Paul F Fitzpatrick; Fiscal Year: 2011
    ....
  6. Augmented Phenylalanine Clearance by Muscles as Novel Therapy for Phenylketonuria
    Cary O Harding; Fiscal Year: 2013
    ....
  7. Genomics and pharmacodynamics of statin-related rhabdomyolysis
    Bruce M Psaty; Fiscal Year: 2013
    ..For validation and translational work, co- investigators will use variants discovered by exome sequencing and replicated by our UK collaborators to conduct basic-science studies and evaluate their function. ..
  8. Engineering a Supplemental Phenylalanine Metabolic Pathway to Prevent mPKU
    Stephen K Hunter; Fiscal Year: 2011
    ..Furthermore, mice will be injected at different time points during pregnancy to evaluate the effects of "boosting" the phenylalanine metabolic pathway with the encapsulated cells at different stages of pregnancy on the pups. ..
  9. Glycolysis and Glutamate Storage into Synaptic Vesicles
    Tetsufumi Ueda; Fiscal Year: 2010
    ..It is hoped that knowledge gained from this research will be of use in creating a new approach to treatment of certain neurological and mental disorders. ..
  10. Tracking conformational states in enzyme catalysts using correlated X-ray scatter
    Sebastian Doniach; Fiscal Year: 2013
    ..CypA is the target of the widely used immunosuppressive cyclosporine. The HIV virus has been shown to use human cyclophilin during its final stages of viral replication. ..
  11. Mothers' Experience of Breastfeeding Infants with Phenylketonuria (PKU)
    SANDRA ANN BANTA WRIGHT; Fiscal Year: 2010
    ....
  12. Dihydropteridine Reductase: Mechanism of Enzyme Action
    Ruel Z B Desamero; Fiscal Year: 2013
    ..Regulation of DHPR became of interest with the discovery of atypical phenylketonuria, a neurological disorder, associated with a defect in tetrahydrobiopterin recycling. ..
  13. Regulation of Phenylalanine Catabolism
    Paul F Fitzpatrick; Fiscal Year: 2013
    ..g., NMR and mass spectroscopy) with measurement of intrinsic rate constants for binding and catalysis in order to provide a more complete understanding of the allosteric regulation of phenylalanine hydroxylase. ..
  14. GENETIC STUDY OF AUTISTIC CHILDREN AND ADOLESCENTS
    Edwin Cook; Fiscal Year: 1999
    ..The statistical methods have been chosen to reduce the change of a false positive result due to population stratification. ..
  15. The Glycoproteinoses: Second International Workshop on Advances in Pathogenesis a
    STEVEN WALKLEY; Fiscal Year: 2007
    ..Enhancement of research on the glycoproteinoses could provide important breakthroughs for the understanding and treatment of not only these diseases but for all genetic brain disorders. [unreadable] [unreadable] [unreadable]..
  16. DEVICE FOR RAPID SCREENING OF PLASMA HOMOCYSTEINE
    MALONNE DAVIES; Fiscal Year: 2002
    ..What is demonstrated with homocysteine and phenylalanine is just the beginning of a large array of clinical analyzers based on microchip CEEC. ..
  17. IMPROVED METHODS OF ADENOVIRUS MEDIATED GENE TRANSFER
    RANDY EISENSMITH; Fiscal Year: 1999
    ..Strategies that are successful in the treatment of the phenylketonuria present in the Pahenu2 mouse should also be applicable to the treatment of may other human metabolic diseases for which there are not representative animal models. ..
  18. BIOLOGICAL OXIDATION OF PHENYLALANINE BY NONHEME IRON
    John Caradonna; Fiscal Year: 2003
    ..Kinetic and mechanistic experiments will be performed to identify the factors that control and regulate iron reduction. ..
  19. SFT FUNCTION AND REGULATION IN HEMOCHROMATOSIS
    Marianne Wessling Resnick; Fiscal Year: 2003
    ..abstract_text> ..
  20. TENTH INTERNATIONAL SYMPOSIUM ON PTERIDINES
    Madhavan Nair; Fiscal Year: 1992
    ....
  21. Non-Viral Vectors for Liver Gene Transfer
    Feng Liu; Fiscal Year: 2006
    ..The therapeutic effects on the metabolic disease on phenylketonuria (PKU) mice, will be examined after the PAH gene transfer using the approach in this proposal. ..
  22. Non-Invasive Blood Phenylalanine Monitor
    ABDEL HALIM GHANEM; Fiscal Year: 2002
    ..abstract_text> ..
  23. MOUSE GENETIC MODELS FOR PHENYLKETONURIA
    William Dove; Fiscal Year: 1993
    ..We are making these mouse mutant models available to laboratories that specialize in the biochemical analysis of mammalian PKU. A number of biological and biomedical investigations become possible, given the salient mutant lines...
  24. Gene therapy for treatment of hemophilia A
    Hans Herweijer; Fiscal Year: 2002
    ..proposed commercial application: not available ..
  25. GENE THERAPY FOR TREATMENT OF HEMOPHILIA B
    Hans Herweijer; Fiscal Year: 1999
    ..PROPOSED COMMERCIAL APPLICATIONS: Vectors and methodology developed under this proposal should enable a gene therapy protocol for hemophilia B. ..
  26. AN ON-SITE STRIP TEST FOR SCREENING OF PHENYLKETONURIA
    AURORA DE CASTRO; Fiscal Year: 1990
    ..The program is attractive as it offers the opportunity to enhance the standard of preventive medical care by providing accurate on-site answers. Because of its simplicity the test could be performed even in underdeveloped countries...
  27. BEHAVIORAL AND HORMONAL RESPONSES TO STRESS IN INFANTS
    Megan Gunnar; Fiscal Year: 1990
    ..The long-term goals are to gain a better understanding of stress and coping in human infants...
  28. ON-SITE STRIP TEST FOR SCREENING OF GALACTOSEMIA
    AURORA DE CASTRO; Fiscal Year: 1990
    ..This program is attractive as this test format will improve preventive medical care in the U.S. and could increase testing in underdeveloped countries...
  29. QUALITY CONTROL TOOL FOR NEWBORN SCREENING BLOOD SAMPLES
    BRIAN CRAINE; Fiscal Year: 2000
    ..These beneficial effects will combine to assure the commercial success of this project in an arena that will represent a large health care market of 4 million patients per year in the United States alone. ..
  30. EFFECTS OF MATERNAL PHENYLKETONURIA ON PREGNANCY OUTCOME
    Richard Koch; Fiscal Year: 2000
    ..Fetal morbidity, with subsequent problems in growth and development, associated with maternal PKU will be assessed in relation to maternal phenylalanine levels. ..
  31. HETEROLOGOUS GENE THERAPY FOR METABOLISM
    Cary Harding; Fiscal Year: 2000
    ..This study will provide important information regarding the choice of target tissue in gene therapy protocols. ..
  32. AAV-MEDIATED GENE THERAPY--INBORN ERRORS OF METABOLISM
    Cary Harding; Fiscal Year: 1999
    ..This proposal will directly compare the effectiveness of liver-directed versus muscle-directed gene therapy for IEMs. ..
  33. DETECTION OF SINGLE BASE MUTATIONS IN RNA MOLECULES
    Frances Smith; Fiscal Year: 1991
    ..Results obtained in these studies should contribute greatly to a better understanding of the genetic heterogeneity of genetic diseases and should also help us to correlate mutations with specific clinical disease patterns...
  34. Gene therapy treatment for severe anemia
    David Lewis; Fiscal Year: 2002
    ..abstract_text> ..
  35. Structure and Function of Feedback Regulator Protein
    Toshie Yoneyama; Fiscal Year: 2004
    ..The knowledge will provide insight into the altered metabolism of BH4 reported in phenylketonuria, Parkinson's disease, familial dystonia, and several vascular diseases. ..
  36. Grb 10 Isoforms and Insulin Signaling
    Feng Liu; Fiscal Year: 2007
    ..The therapeutic effects on the metabolic disease, phenylketonuria (PKU), will be examined after the PAH gene transfer using the approach in this proposal. ..
  37. The development of monkey models for the study of autism
    LOREN MARTIN; Fiscal Year: 2005
    ..abstract_text> ..
  38. PATHOPHYSIOLOGY OF PKU
    CHARISSA DYER; Fiscal Year: 2001
    ..The investigator will employ histochemical, immunohistochemical, molecular, and biochemical techniques to better understand the pathophysiology of PKU, and ultimately lead to the development of additional therapies for PKU. ..
  39. SEROTONIN RECEPTORS IN PHENYLKETONURIC RATS
    Justus Ike; Fiscal Year: 2000
    ..The findings of this work may contribute toward an understanding of the mechanisms involved in this disease. ..
  40. National PKU Alliance 2014 &2016 Conference - Scientific Exchange
    CHRISTINE SCHLEGEL BROWN; Fiscal Year: 2013
    ..Funding is requested to assist with the implementation of the Scientific Exchange portion of the overall conference. ..
  41. NEONATAL BIOCHEMICAL DISTURBANCES AND ADULT COGNITION
    Barbara Strupp; Fiscal Year: 1990
    ..Second, determining the pathogenesis of HP-induced cognitive dysfunction is critical for improving the treatment of phenylketonuria, a genetic disease that produces both HP and permanent mental retardation...
  42. Intravenous non-viral gene therapy for phenylketonuria (PKU)
    Cary Harding; Fiscal Year: 2006
    ..co-administration of 3 separate plasmid vectors encoding single genes. These preclinical trials will form the basis for the development of future clinical trials in humans with PKU. [unreadable] [unreadable] [unreadable] [unreadable]..
  43. AAV2/8 vector-mediated liver gene therapy for phenylketonuria (PKU)
    Cary Harding; Fiscal Year: 2009
    ..We propose that lessons learned from the treatment of murine PKU will ultimately be applicable to the treatment of human PKU and other allied IEM. ..
  44. Stem Cell-Mediated Liver Repopulation for Murine PKU
    Cary Harding; Fiscal Year: 2006
    ..The overall goal of the project is to explore HSC-mediated liver repopulation as treatment for rare inborn errors of metabolism using murine PKU as a model system. [unreadable] [unreadable] [unreadable]..
  45. Phenylalanine Hydroxylase Deficiency: Response to BH4
    Reuben Matalon; Fiscal Year: 2002
    ..Treatment with BH4 should lead to a better outcome for PKU patients and for maternal PKU. ..
  46. KNOCKOUT MODEL FOR CANAVAN DISEASE
    Reuben Matalon; Fiscal Year: 2001
    ..5) The knock-out mouse will be used in future studies for determining the metabolic role of NAA in brain, for experimentation with enzyme therapy and gene therapy. ..
  47. RESPONSE OF PHENYLKETONURIA TO TETRAHYDROBIOPTERIN (BH4)
    Reuben Matalon; Fiscal Year: 2007
    ..Abstract Not Provided ..
  48. THE CARNITINE TRANSPORTER IN HUMAN DISEASE
    Nicola Longo; Fiscal Year: 2010
    ....
  49. EXPANDED NEWBORN SCREENING FOR METABOLIC DISORDERS
    Susan Waisbren; Fiscal Year: 2006
    ..Primary data from parent interviews and the New England Newborn Screening Program, as well as secondary data from published reports and a panel of experts will be used as inputs to the cost-effectiveness model. [unreadable] [unreadable]..
  50. Anaplerotic therapy in Propionic Acidemia
    Nicola Longo; Fiscal Year: 2008
    ..This approach, if effective, could be extended to a number of other diseases, including other organic acidemias and mitochondrial disorders. [unreadable] [unreadable] [unreadable]..
  51. Genotype Analysis for Diagnosis of Urea Cycle Disorders
    Steven Dobrowolski; Fiscal Year: 2007
    ..The proposed assay panels provide a means to readily assess gene that are well established to contribute to hyperammonemia. [unreadable] [unreadable] [unreadable]..
  52. FilmArray-A Closed System for Multi-Pathogen Screening
    Steven Dobrowolski; Fiscal Year: 2005
    ..Pouches are designed to assay for candidate infectious agents consistent with clinical presentation. ..
  53. Dietary Control of PKU with Glycomacropeptide from Whey
    Denise Ney; Fiscal Year: 2007
    ..Data will help plan an outpatient clinical trial to determine if ingestion of a low-phe GMP diet will improve dietary adherence and metabolic control. ..