Dermatologic Manifestations of Phenylketonuria Medication

  • Author: Zeljko P Mijuskovic, MD, PhD; Chief Editor: Dirk M Elston, MD   more...
 
Updated: Aug 15, 2011
 

Medication Summary

The goals of pharmacotherapy are to reduce morbidity and to prevent complications. An alternative enzyme therapy for phenylketonuria (PKU) has undergone trials, which involve the substitution of PAH with Phe ammonialyase, a non-cofactor – dependent plant protein involved in Phe degradation. It is currently under investigation for the potential treatment of patients with PKU who do not respond to BH4.

Research into gene therapy for the treatment of PKU has been ongoing over the last 2 decades. The focus has been on replacement of the human PAH mutant gene in somatic cells of PKU patients, because germ-line therapy, which is the most desirable and ultimate solution, still faces ethical and technical barriers.[11]

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Pteridines

Class Summary

Clinical trials have shown that a subset of classic PKU children respond to BH4 therapy, dependent upon their PAH gene mutation.

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Sapropterin (Kuvan)

 

Synthetic form of (BH4), the cofactor for the enzyme PAH. PAH hydroxylates Phe through an oxidative reaction to form tyrosine. PAH activity is absent or deficient in patients with PKU. Treatment with BH4 can activate residual PAH enzyme, improve normal oxidative metabolism of Phe, and decrease Phe levels in some patients. Indicated to reduce blood Phe levels in patients with hyperphenylalaninemia caused by BH4 -responsive PKU. Used in conjunction with a Phe-restricted diet.

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Drugs acting at the blood-brain barrier

Class Summary

Because some patients are not able to adhere rigorously to the Phe-restricted diet during life, alternative treatment regimens have been developed.[12]

Large neutral amino acids (PhenylAde, PreKunil)

 

Tab contains essential amino acids (LNAAs), including high dosages of tyrosine and tryptophan. Too much tyrosine can cause headaches, which limits the numbers of tabs that can be consumed. Furthermore, by competitive inhibition, they also counteract uptake of Phe across the blood-brain barrier, thus reducing its impairing effect on neurotransmitter production.

The main purpose of the tabs is to create a Phe-blocking effect.

May be ideal for young adults, when compliance is poor, and for late-diagnosed patients, in whom compliance is low and in whom drinking formula can be a burden for the patient and caretakers.

Young women of childbearing age need to realize this drug does not protect their fetus from the teratogenic effects of Phe.

Tabs must be combined with a certain amount of natural protein in order for the diet to contain sufficient protein.

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Contributor Information and Disclosures
Author

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.

Coauthor(s)

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.

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

Disclosure: Nothing to disclose.

Specialty Editor Board

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.

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.

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.

Catherine M Quirk, MD  Clinical Assistant Professor, Department of Dermatology, University of Pennsylvania

Catherine M Quirk, MD is a member of the following medical societies: Alpha Omega Alpha and American Academy of Dermatology

Disclosure: Nothing to disclose.

Chief Editor

Dirk M Elston, MD  Director, Ackerman Academy of Dermatopathology, New York

Dirk M Elston, MD is a member of the following medical societies: American Academy of Dermatology

Disclosure: Nothing to disclose.

Acknowledgments

The authors and editors of eMedicine gratefully acknowledge the contributions of previous Chief Editor, William D. James, MD, to the development and writing of this article.

References

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  17. Macdonald A, Davies P, Daly A, 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].

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Fair skin and hair resulting from impairment of melanin synthesis.
 
 
 
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