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Phenylketonuria Clinical Presentation

  • Author: Georgianne L Arnold, MD; Chief Editor: Luis O Rohena, MD  more...
 
Updated: Apr 28, 2014
 

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
    Fair skin and hair resulting from impairment of meFair skin and hair resulting from impairment of melanin synthesis.
  • 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[1]

Other manifestations of untreated PKU are as follows:

  • Intellectual disability (the most common finding overall)
  • Musty or mousy odor
  • Epilepsy (50%)[2]
  • 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

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 and Genomics, Society for Inherited Metabolic Disorders, Society for the Study of Inborn Errors of Metabolism, American Society of Human Genetics

Disclosure: Received grant/research funds from Biomarin for clinical trial.

Coauthor(s)

Robert D Steiner, MD Chief Medical Officer, Acer Therapeutics; Clinical Professor, University of Wisconsin School of Medicine and Public Health

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 and Genomics, American Society of Human Genetics, Society for Inherited Metabolic Disorders, Society for Pediatric Research, Society for the Study of Inborn Errors of Metabolism

Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: Acer Therapeutics; Retrophin; Raptor Pharma; Veritas Genetics; Censa Pharma<br/>Received income in an amount equal to or greater than $250 from: Acer Therapeutics; Retrophin; Raptor Pharma; Censa Pharma.

Chief Editor

Luis O Rohena, MD Chief, Medical Genetics, San Antonio Military Medical Center; Assistant Professor of Pediatrics, Uniformed Services University of the Health Sciences, F Edward Hebert School of Medicine; Assistant Professor of Pediatrics, University of Texas Health Science Center at San Antonio

Luis O Rohena, MD is a member of the following medical societies: American Academy of Pediatrics, American Chemical Society, American College of Medical Genetics and Genomics, American Society of Human Genetics

Disclosure: Nothing to disclose.

Acknowledgements

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.

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