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Phenylketonuria

  • Reference work entry
Atlas of Genetic Diagnosis and Counseling

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Classical phenylketonuria (PKU) is a rare metabolic disorder, resulting from a deficiency of a liver enzyme, phenylalanine hydroxylase. The deficiency of the enzyme leads to elevated phenylalanine (Phe) levels in the blood and various tissues including the brain. The incidence in Caucasians is approximately one in 10,000, giving a heterozygote frequency of one in 50 to one in 70. About one in 15,000 infants is born with PKU in the United States.

Synonyms and Related Disorders

Hyperphenylalaninemia; Phenylalanine hydroxylase deficiency; PKU

Genetics/Basic Defects

  1. 1.

    Inheritance

    1. a.

      Autosomal recessive

    2. b.

      Parents: obligatory carriers

  2. 2.

    Basic defect

    1. a.

      Deficient activity of the enzyme phenylalanine hydroxylase (PAH), resulting in hyperphenylalaninemia. PAH, a liver-specific enzyme, catalyzes the conversion of phenylalanine to tyrosine, using tetrahydrobiopterin as a cofactor. Chromosomal locus of the PAH gene is on 12q24.1.

    2. b.

      Identification of more than 400 different mutations in the PAH...

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References

  • American Academy of Pediatrics Committee on Genetics. (2001). Maternal phenylketonuria. Pediatrics, 107, 427–428.

    Article  Google Scholar 

  • Baumeister, A. A., & Baumeister, A. A. (1998). Dietary treatment of destructive behavior associated with hyperphenylalaninaemia. Clinical Neuropharmacology, 21, 18–27.

    PubMed  CAS  Google Scholar 

  • Brown, M. C. J., & Guest, J. F. (1999). Economic impact of feeding a phenylalanine-restricted diet to adults with previously untreated phenylketonuria. Journal of Intellectual Disability Research, 43, 30–37.

    Article  PubMed  Google Scholar 

  • Centerwall, S. A., & Centerwall, W. R. (2000). The discovery of phenylketonuria: The story of a young couple, two retarded children, and a scientist. Pediatrics, 105, 89–103.

    Article  PubMed  CAS  Google Scholar 

  • Clarke, T. R. (2003). The maternal phenylketonuria: A summary of progress and challenges for the future. Pediatrics, 112, 1584–1587.

    Article  PubMed  Google Scholar 

  • Cleary, M. A., Walter, J. H., Wraight, J. E., et al. (1994). Magnetic resonance imaging in phenylketonuria. Lancet, 344, 87–90.

    Article  PubMed  CAS  Google Scholar 

  • Di Meglio, G. (1998). Phenylketonuria. Pediatrics in Review, 19, 214–215.

    Article  Google Scholar 

  • Dougherty, F. E., & Levy, H. L. (1999). Present newborn screening for phenylketonuria. Mental Retardation and Developmental Disabilities Research Reviews, 5, 144–149.

    Article  Google Scholar 

  • Dyer, C. A. (1999). Pathophysiology of phenylketonuria. Mental Retardation and Developmental Disabilities Research Reviews, 5, 104–112.

    Article  Google Scholar 

  • Dyer, C. A., Kendler, A., Philibotte, T., et al. (1996). Evidence for central nervous system glial cell plasticity in phenylketonuria. Journal of Neuropathology and Experimental Neurology, 55, 795–814.

    Article  PubMed  CAS  Google Scholar 

  • Eisensmith, R. C., Martinez, D. R., Kuzmin, A. I., et al. (1996). Molecular basis of phenylketonuria and a correlation between genotype and phenotype in a heterogeneous Southeastern US population. Pediatrics, 97, 512–516.

    PubMed  CAS  Google Scholar 

  • Feillet, F., & Agostoni, C. (2010). Nutritional issues in treating phenylketonuria. Journal of Inherited Metabolic Disease [Published Online].

    Google Scholar 

  • Fitzgerald, B., Morgan, J., Keene, N., et al. (2000). An investigation into diet treatment for adults with previously untreated phenylketonuria and severe intellectual disability. Journal of Intellectual Disability Research, 44, 53–59.

    Article  PubMed  Google Scholar 

  • Grosse, S. D. (2010). Late-treated phenylketonuria and partial reversibility of intellectual impairment. Child Development, 81, 200–211.

    Article  PubMed  Google Scholar 

  • Güttler, F., Azen, C., Guldberg, P., et al. (1999). Relationship among genotype, biochemical phenotype, and cognitive performance in females with phenylalanine hydroxylase deficiency: Report from the Maternal Phenylketonuria Collaborative Study. Pediatrics, 104, 258–262.

    Article  PubMed  Google Scholar 

  • Güttler, F., Azen, C., Guldberg, P., et al. (2003). Impact of the phenylalanine hydroxylase gene on maternal phenylketonuria outcome. Pediatrics, 112, 1530–1533.

    PubMed  Google Scholar 

  • Güttler, F., Guldberg, P., Eisensmith, R. C., et al. (1999). Molecular genetics and outcome in PKU. Mental Retardation and Developmental Disabilities Research Reviews, 5, 113–116.

    Article  Google Scholar 

  • Hanley, W. B., Platt, L. D., Bachman, R. P., et al. (1999). Undiagnosed maternal phenylketonuria: The need for prenatal selective screening or case finding. American Journal of Obstetrics and Gynecology, 180, 986–994.

    Article  PubMed  CAS  Google Scholar 

  • Hellekson, K. L. (2001). NIH consensus statement on phenylketonuria. American Family Physician, 63, 1430–1432.

    PubMed  CAS  Google Scholar 

  • Hoeks, M. P. A., den Heijer, M., & Janssen, M. C. H. (2009). Adult issues in phenylketonuria. Netherlands Journal of Medicine, 67, 1–7.

    Google Scholar 

  • Howell, R. R., Chakravarti, A., Dawson, G., et al. (2001). National institutes of health consensus development conference statement: Phenylketonuria: Screening and management, October 16–18, 2000. Pediatrics, 108(4), 972–982.

    Article  Google Scholar 

  • Hvas, A. M., Nexo, E., & Nielsen, J. B. (2006). Vitamin B12 and vitamin B6 supplementation is needed among adults with phenylketonuria. Journal of Inherited Metabolic Disease, 29, 47–53.

    Article  PubMed  CAS  Google Scholar 

  • Joseph, B., & Dyer, C. A. (2003). Relationship between myelin production and dopamine synthesis in the PKU mouse brain. Journal of Neurochemistry, 86, 615–626.

    Article  PubMed  CAS  Google Scholar 

  • Kalsner, L. R., Rohr, F. J., Strauss, K. A., et al. (2001). Tyrosine supplementation in phenylketonuria: Diurnal blood tyrosine levels and presumptive brain influx of tyrosine and other large neutral amino acids. Journal of Pediatrics, 139, 421–427.

    Article  PubMed  CAS  Google Scholar 

  • Koch, R. K. (1999). Issues in newborn screening for phenylketonuria. American Family Physician, 605, 1462–1466.

    Google Scholar 

  • Koch, R., Hanley, W., Levy, H., et al. (2003). The maternal phenylketonuria international study: 1984–2002. Pediatrics, 112, 1523–1529.

    PubMed  Google Scholar 

  • Landolt, M. A., Nuoffer, J.-M., Steinmann, B., et al. (2002). Quality of life and psychologic adjustment in children and adolescents with early treated phenylketonuria can be normal. Journal of Pediatrics, 140, 516–521.

    Article  PubMed  Google Scholar 

  • Levy, H. L., & Ghavami, M. (1996). Maternal phenylketonuria: A metabolic teratogen. Teratology, 53, 176–184.

    Article  PubMed  CAS  Google Scholar 

  • Levy, H. L., Lobbregt, D., Barnes, P. D., et al. (1996). Maternal phenylketonuria: Magnetic resonance imaging of the brain in offspring. Journal of Pediatrics, 128, 770–775.

    Article  PubMed  CAS  Google Scholar 

  • Levy, H. L., Lobbregt, D., Platt, L. D., et al. (1996). Fetal ultrasonography in maternal PKU. Prenatal Diagnosis, 16, 599–604.

    Article  PubMed  CAS  Google Scholar 

  • Mabry, C. C. (1990). Phenylketonuria: Contemporary screening and diagnosis. Annals of Clinical and Laboratory Science, 20, 393–397.

    PubMed  CAS  Google Scholar 

  • Matalon, R., & Michals, K. (1991). Phenylketonuria: Screening, treatment and maternal PKU. Clinical Biochemistry, 24, 337–342.

    Article  PubMed  CAS  Google Scholar 

  • Maternal Phenylketonuria Collaborative Study (MPKUCS) Offspring. (1997). Facial anomalies, malformations, and early neurological sequelae. American Journal of Medical Genetics, 69, 89–95.

    Article  Google Scholar 

  • Meglio, G. D. (1998). Phenylketonuria. Pediatrics in Review, 19, 214–215.

    Article  Google Scholar 

  • Mitchell, J. J., & Scriver, C. R. (2010). Phenylalanine hydroxylase deficiency. GeneReviews. Updated May 4, 2010. Available at: http://www.ncbi.nlm.nih.gov/books/NBK1504/

  • Moats, R. A., Scadeng, M., & Nelson, M. D., Jr. (1999). MR imaging and spectroscopy in PKU. Mental Retardation and Developmental Disabilities Research Reviews, 5, 132–135.

    Article  Google Scholar 

  • Modan-Moses, D., Vered, I., Schwartz, G., et al. (2007). Peak bone mass in patients with phenylketonuria. Journal of Inherited Metabolic Disease, 30, 202–208.

    Article  PubMed  CAS  Google Scholar 

  • National Institutes of Health Consensus Development Panel; National Institutes of Health Consensus Development Conference Statement (2001). Phenylketonuria: screening and management, October 16–18, 2000. Pediatrics. 108, 972–982.

    Google Scholar 

  • Paine, R. S. (1957). The variability in manifestations of untreated patients with phenylketonuria. Pediatrics, 20, 290–302.

    PubMed  CAS  Google Scholar 

  • Pietz, J., Dunckelmann, R., Rupp, A., et al. (1998). Neurological outcome in adult patients with early-treated phenylketonuria. European Journal of Pediatrics, 157, 824–830.

    Article  PubMed  CAS  Google Scholar 

  • Pietz, J., Fatkenheuer, B., Burgard, P., et al. (1997). Psychiatric disorders in adult patients with early-treated phenylketonuria. Pediatrics, 99, 345–350.

    Article  PubMed  CAS  Google Scholar 

  • Platt, L. D., Koch, R., Hanley, W. B., et al. (2000). The international study of pregnancy outcome in women with maternal phenylketonuria: Report of a 12-year study. American Journal of Obstetrics and Gynecology, 182, 326–333.

    Article  PubMed  CAS  Google Scholar 

  • Restrepo, S., Aguero, H., Jayakar, P., et al. (1999). Clinical findings in untreated classic phenylketonuria. International Pediatrics, 14, 232–234.

    Google Scholar 

  • Robinson, M., White, F., Cleary, M. A., et al. (2002). Increased risk of vitamin B12 deficiency in patients with phenylketonuria on an unrestricted or relaxed diet. Journal of Pediatrics, 136, 545–547.

    Google Scholar 

  • Rouse, B., Azen, C., Koch, R., et al. (1997). Maternal phenylketonuria collaborative study (MPKUCS) offspring: facial anomalies, malformations, and early neurological sequelae. American Journal of Medical Genetics, 69, 89–95.

    Article  PubMed  CAS  Google Scholar 

  • Rouse, B., Matalon, R., Koch, R., et al. (2000). Maternal phenylketonuria syndrome: Congenital heart defects, microcephaly, and developmental outcomes. Journal of Pediatrics, 136(1), 57–61.

    Article  PubMed  CAS  Google Scholar 

  • Schoonheyt, W. E., Clarke, J. T., Hanley, W. B., et al. (1994). Feto-maternal plasma phenylalanine concentration gradient from 19 weeks gestation to term. Clinica Chimica Acta, 225, 165–169.

    Article  CAS  Google Scholar 

  • Scriver, C. R., & Kaufman, S. (2001). Hyperphenylalaninemia: Phenylalanine hydroxylase deficiency. In C. R. Scriver, A. L. Beaudet, W. S. Sly, & D. Valle (Eds.), The metabolic & molecular bases of inherited disease (8th ed., pp. 1667–1724). New York: McGraw-Hill (Chap. 77).

    Google Scholar 

  • Sener, R. N. (2003). Diffusion MRI findings in phenylketonuria. European Radiology, 13, 226–229.

    Article  Google Scholar 

  • Sinai, L. N., Kim, S. C., Casey, R., et al. (1995). Phenylketonuria screening: Effect of early newborn discharge. Pediatrics, 96, 605–608.

    PubMed  CAS  Google Scholar 

  • Thompson, A. J., Smith, I., Youl, B. D., et al. (1990). Neurological deterioration in young adults with phenylketonuria. Lancet, 336, 602–605.

    Article  PubMed  CAS  Google Scholar 

  • Waisbren, S. E. (1999). Developmental and neuropsychological outcome in children born to mothers with phenylketonuria. Mental Retardation and Developmental Disabilities Research Reviews, 5, 125–131.

    Article  Google Scholar 

  • Weglage, J., Funders, B., Wilken, B., et al. (1993). School performance and intellectual outcome in adolescents with phenylketonuria. Acta Paediatrica, 81, 582–586.

    Article  Google Scholar 

  • Yannicelli, S., & Ryan, A. (1995). Improvements in behaviour and physical manifestations in previously untreated adults with phenylketonuria using a phenylalanine-restricted diet: A national survey. Journal of Inherited Metabolic Disease, 18, 131–134.

    Article  PubMed  CAS  Google Scholar 

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Editor information

Editors and Affiliations

  1. Perinatal and Clinical Genetics, Department of Pediatrics, LSU Health Sciences Center, 1501 Kings Highway, Shreveport, LA, 71130, USA

    Harold Chen

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(2012). Phenylketonuria. In: Chen, H. (eds) Atlas of Genetic Diagnosis and Counseling. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-1037-9_191

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