Phenylketonuria Workup

  • Author: Robert D Steiner, MD; Chief Editor: Bruce Buehler, MD   more...
 
Updated: Nov 23, 2011
 

Approach Considerations

Older textbooks and protocols occasionally called for phenylalanine-loading studies to help determine if a child with phenylketonuria (PKU) still required phenylalanine restriction after 1 or more years; however, as the treatment range for phenylalanine levels has decreased, these studies generally have been abandoned.

A qualified laboratory should measure plasma phenylalanine and tyrosine. A qualified laboratory should perform blood and urine analysis of biopterin and neopterins in order to rule out defects of biopterin synthesis or recycling. DNA mutation analysis is adjunctive, and it is reasonable to perform urine organic acid analysis.

Prenatal diagnosis is available but rarely used since the disorder is so treatable. Prenatal diagnosis can be accomplished more readily by DNA mutation analysis following chorionic villous sampling or amniocentesis.

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Laboratory Studies

Perform screening on blood samples during the first week of life. Wide variability in phenylalanine concentrations in a 24-hour period in children with PKU may necessitate repeat screening. Screening for PKU involves the following:

  • Determination of phenylalanine levels, the standard amino acid analysis done by means of ion exchange chromatography or tandem mass spectrometry
  • The Guthrie test as a bacterial inhibition assay; formerly used, now being replaced by tandem mass spectrometry

Further measures may be indicated, depending on the results of screening:

  • Abnormal newborn screening results require immediate follow-up in accordance with local regulations.
  • Low-grade elevations of phenylalanine may require repeat screening
  • More significant elevations may require definitive testing and referral to a metabolic treatment facility experienced with PKU
  • Late diagnoses are usually made during amino acid analysis of individuals who are developmentally abnormal

Results of urine tests (ie, ferric chloride test) may be negative in the first month of life and are rarely used in current practice. Perform blood and urine analysis of biopterin and neopterins to exclude defects of biopterin synthesis or recycling.

Follow nutritional adequacy on a regular basis because deficiencies of iron, vitamins, selenium, protein, essential fatty acids, and other nutrients have been reported in patient with treated PKU.

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Magnetic Resonance Imaging

Cranial MRI studies may be indicated in older individuals who have abandoned the diet and are experiencing deficits in motor or cognitive function, or when there are behavioral, cognitive, or psychiatric concerns. Areas of demyelination are common. These areas appear to be related to both higher phenylalanine levels in the blood and brain and to poorer cognitive outcome. In terms of volume loss, the most severely affected brain structures are the cerebrum, the corpus callosum, the hippocampus, and the pons.[11]

Preliminary indications suggest that brain phenylalanine levels can be measured by means of cranial magnetic resonance spectroscopy (MRS) and that these levels may be more predictive of outcome than blood phenylalanine levels are. However, this work is done in only a few centers, and there is some controversy surrounds whether such state-of-the-art technology is useful.

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Contributor Information and Disclosures
Author

Robert D Steiner, MD  Credit Unions for Kids Professor of Pediatric Research, Professor of Pediatrics and Molecular and Medical Genetics, Vice Chair for Research, Department of Pediatrics, Faculty, Program in Molecular and Cellular Biosciences, Oregon Health and Science University School of Medicine; Attending Physician, Doernbecher Children's Hospital; Staff Consultant, Director of Metabolic Bone Disease Clinic, Shriners Hospital Portland

Robert D Steiner, MD is a member of the following medical societies: American Academy of Pediatrics, American Association for the Advancement of Science, American College of Medical Genetics, American Society of Human Genetics, Oregon Medical Association, Society for Inherited Metabolic Disorders, Society for Pediatric Research, Society for the Study of Inborn Errors of Metabolism, and Western Society for Pediatric Research

Disclosure: Amicus Honoraria Consulting; Actelion Honoraria Consulting; Actelion Honoraria Speaking and teaching; Biomarin Honoraria Consulting; Genzyme Honoraria Consulting; Shire Honoraria Consulting

Coauthor(s)

Georgianne L Arnold, MD  Faculty, Department of Pediatrics, Divison of Genetics, University of Pittsburgh School of Medicine

Georgianne L Arnold, MD is a member of the following medical societies: American College of Medical Genetics, American Society of Human Genetics, Society for Inherited Metabolic Disorders, and Society for the Study of Inborn Errors of Metabolism

Disclosure: Biomarin Grant/research funds clinical trial

Chief Editor

Bruce Buehler, MD  Professor, Department of Pediatrics and Genetics, Director RSA, University of Nebraska Medical Center

Bruce Buehler, MD is a member of the following medical societies: American Academy for Cerebral Palsy and Developmental Medicine, American Academy of Pediatrics, American Association on Mental Retardation, American College of Medical Genetics, American College of Physician Executives, American Medical Association, and Nebraska Medical Association

Disclosure: Nothing to disclose.

Additional Contributors

David F Butler, MD Professor of Dermatology, Texas A&M University College of Medicine; Chair, Department of Dermatology, Director, Dermatology Residency Training Program, Scott and White Clinic, Northside Clinic

David F Butler, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American Medical Association, American Society for Dermatologic Surgery, American Society for MOHS Surgery, Association of Military Dermatologists, and Phi Beta Kappa

Disclosure: Nothing to disclose.

Mark A Crowe, MD Assistant Clinical Instructor, Department of Medicine, Division of Dermatology, University of Washington School of Medicine

Mark A Crowe, MD is a member of the following medical societies: American Academy of Dermatology and North American Clinical Dermatologic Society

Disclosure: Nothing to disclose.

William D James, MD, Paul R Gross Professor of Dermatology, University of Pennsylvania School of Medicine; Vice-Chair, Program Director, Department of Dermatology, University of Pennsylvania Health System

William D James, MD is a member of the following medical societies: American Academy of Dermatology, and the Society for Investigative Dermatology.

Disclosure: Royalty from Elselvier.

Djordjije Karadaglic, MD, DSc Professor, School of Medicine, University of Podgorica, Podgorica, Montenegro

Djordjije Karadaglic, MD, DSc is a member of the following medical societies: American Academy of Dermatology, European Academy of Dermatology and Venereology, and Serbian Association of DermatoVenereologists

Disclosure: Nothing to disclose

Zeljko P Mijuskovic, MD, PhD Associate Professor of Dermatology, Department of Dermatology and Venereology, Military Medical Academy, Serbia

Zeljko P Mijuskovic, MD, PhD is a member of the following medical societies: European Academy of Dermatology and Venereology, European Society for Dermatological Research, International Society of Dermatology, and Serbian Association of DermatoVenereologists

Disclosure: Nothing to disclose.

Christian J Renner, MD Consulting Staff, Department of Pediatrics, University Hospital for Children and Adolescents, Erlangen, Germany

Disclosure: Nothing to disclose.

Robert A Schwartz, MD, MPH Professor and Head, Dermatology, Professor of Pathology, Pediatrics, Medicine, and Preventive Medicine and Community Health, University of Medicine and Dentistry of New Jersey-New Jersey Medical School

Robert A Schwartz, MD, MPH is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American College of Physicians, and Sigma Xi

Disclosure: Nothing to disclose.

Ljubomir Stojanov, MD, PhD Lecturer in Metabolism and Clinical Genetics, University of Belgrade School of Medicine, Serbia

Disclosure: Nothing to disclose.

Mary L Windle, PharmD, Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

References

  1. Donati A, Vincenzi C, Tosti A. Acute hair loss in phenylketonuria. J Eur Acad Dermatol Venereol. May 2009;23(5):613-5. [Medline].

  2. Santos LL, Castro-Magalhães M, Fonseca CG, Starling AL, Januário JN, Aguiar MJ, et al. PKU in Minas Gerais State, Brazil: mutation analysis. Ann Hum Genet. Nov 2008;72:774-9. [Medline].

  3. Stojiljkovic M, Jovanovic J, Djordjevic M, Grkovic S, Cvorkov Drazic M, Petrucev B, et al. Molecular and phenotypic characteristics of patients with phenylketonuria in Serbia and Montenegro. Clin Genet. Aug 2006;70(2):151-5. [Medline].

  4. Guldberg P, Henriksen KF, Sipilä I, Güttler F, de la Chapelle A. Phenylketonuria in a low incidence population: molecular characterisation of mutations in Finland. J Med Genet. Dec 1995;32(12):976-8. [Medline]. [Full Text].

  5. Williams RA, Mamotte CD, Burnett JR. Phenylketonuria: an inborn error of phenylalanine metabolism. Clin Biochem Rev. Feb 2008;29(1):31-41. [Medline]. [Full Text].

  6. Bosch AM, Tybout W, van Spronsen FJ, de Valk HW, Wijburg FA, Grootenhuis MA. The course of life and quality of life of early and continuously treated Dutch patients with phenylketonuria. J Inherit Metab Dis. Feb 2007;30(1):29-34. [Medline].

  7. Macdonald A, Davies P, Daly A, Hopkins V, Hall SK, Asplin D, et al. Does maternal knowledge and parent education affect blood phenylalanine control in phenylketonuria?. J Hum Nutr Diet. Aug 2008;21(4):351-8. [Medline].

  8. Lee PJ, Ridout D, Walter JH, Cockburn F. Maternal phenylketonuria: report from the United Kingdom Registry 1978-97. Arch Dis Child. Feb 2005;90(2):143-6. [Medline]. [Full Text].

  9. Martynyuk AE, Ucar DA, Yang DD, Norman WM, Carney PR, Dennis DM, et al. Epilepsy in phenylketonuria: a complex dependence on serum phenylalanine levels. Epilepsia. Jun 2007;48(6):1143-50. [Medline].

  10. Cleary MA, Walter JH, Wraith JE, Jenkins JP, Alani SM, Tyler K, et al. Magnetic resonance imaging of the brain in phenylketonuria. Lancet. Jul 9 1994;344(8915):87-90. [Medline].

  11. Sarkissian CN, Gámez A, Scriver CR. What we know that could influence future treatment of phenylketonuria. J Inherit Metab Dis. Feb 2009;32(1):3-9. [Medline].

  12. Yannicelli S, Ryan A. Improvements in behaviour and physical manifestations in previously untreated adults with phenylketonuria using a phenylalanine-restricted diet: a national survey. J Inherit Metab Dis. 1995;18(2):131-4. [Medline].

  13. Bekhof J, van Rijn M, Sauer PJ, Ten Vergert EM, Reijngoud DJ, van Spronsen FJ. Plasma phenylalanine in patients with phenylketonuria self-managing their diet. Arch Dis Child. Feb 2005;90(2):163-4. [Medline]. [Full Text].

  14. Sarkissian CN, Gámez A, Wang L, Charbonneau M, Fitzpatrick P, Lemontt JF, et al. Preclinical evaluation of multiple species of PEGylated recombinant phenylalanine ammonia lyase for the treatment of phenylketonuria. Proc Natl Acad Sci U S A. Dec 30 2008;105(52):20894-9. [Medline]. [Full Text].

  15. Burton BK, Grange DK, Milanowski A, et al. The response of patients with phenylketonuria and elevated serum phenylalanine to treatment with oral sapropterin dihydrochloride (6R-tetrahydrobiopterin): a phase II, multicentre, open-label, screening study. J Inherit Metab Dis. Oct 2007;30(5):700-7. [Medline].

  16. Ounap K, Lilleväli H, Metspalu A, Lipping-Sitska M. Development of the phenylketonuria screening programme in Estonia. J Med Screen. 1998;5(1):22-3. [Medline].

  17. Pietz J, Kreis R, Rupp A, Mayatepek E, Rating D, Boesch C, et al. Large neutral amino acids block phenylalanine transport into brain tissue in patients with phenylketonuria. J Clin Invest. Apr 1999;103(8):1169-78. [Medline]. [Full Text].

  18. Maillot F, Lilburn M, Baudin J, Morley DW, Lee PJ. Factors influencing outcomes in the offspring of mothers with phenylketonuria during pregnancy: the importance of variation in maternal blood phenylalanine. Am J Clin Nutr. Sep 2008;88(3):700-5. [Medline].

  19. Waisbren SE, Noel K, Fahrbach K, Cella C, Frame D, Dorenbaum A, et al. Phenylalanine blood levels and clinical outcomes in phenylketonuria: a systematic literature review and meta-analysis. Mol Genet Metab. Sep-Oct 2007;92(1-2):63-70. [Medline].

 
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Phenylalanine hydroxylase converts phenylalanine to tyrosine.
Fair skin and hair resulting from impairment of melanin synthesis.
 
 
 
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