Phenylketonuria Clinical Presentation

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

History

Most individuals with phenylketonuria (PKU) appear normal at birth. If newborn screening fails, progressive developmental delay is the most common presentation. Other findings in untreated children in later infancy and childhood may include vomiting, mousy odor, eczema, seizures, self-mutilation, and severe behavioral disorders.

Older individuals who cease dietary treatment in childhood may have evidence of demyelination on MRI. Occasionally, deterioration of cognitive performance or motor skills also may be present. Intelligence quotients (IQs) may drop by 10 points or more if the diet is stopped in midchildhood.

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Physical Examination

The clinical manifestations of PKU are largely of historical interest, because the damaging features of the disease are virtually always prevented through early diagnosis and treatment. Skin findings are as follows:

  • Fair skin and hair – This is the most characteristic skin manifestation, resulting from impairment of melanin synthesis (see the image below); it can be striking in black and Japanese patients, although not all untreated patients are fair, and treated patients often have typical pigmentation
  • Eczema (including atopic dermatitis)
  • Light sensitivity
  • Increased incidence of pyogenic infections
  • Increased incidence of keratosis pilaris
  • Decreased number of pigmented nevi
  • Sclerodermalike plaques
  • Hair loss[9] Fair skin and hair resulting from impairment of meFair skin and hair resulting from impairment of melanin synthesis.

Other manifestations of untreated PKU are as follows:

  • Intellectual disability (the most common finding overall)
  • Musty or mousy odor
  • Epilepsy (50%)[10]
  • Extrapyramidal manifestations (eg, parkinsonism)
  • Eye abnormalities (eg, hypopigmentation)
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Complications

Subtle attention and performance deficits in organization and planning persist in treated patients. These deficits are in some cases related to phenylalanine levels and may interfere with academic achievement.

A few patients experience psychological problems, including poor self-esteem. Agoraphobia and more severe problems have been described, especially in women who have discontinued the treatment. Because phenylalanine competes with tryptophan (the precursor of serotonin) for entry into the brain, psychological symptoms may have a biological basis and improved dietary control is recommended.

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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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