Hyperphenylalaninemia Clinical Presentation

  • Author: Georgianne L Arnold, MD; Chief Editor: Bruce Buehler, MD   more...
 
Updated: Mar 1, 2012
 

History

An abnormal newborn screen is the most common history in patients with hyperphenylalaninemia. Infants are screened for elevated phenylalanine in every US state and in Puerto Rico. Several other countries also have established screening programs.

Affected individuals missed by screening may have mild-to-moderate performance deficits, depending on the degree of phenylalanine elevation.

At phenylalanine levels near 20 mg/dL, phenylketonuria (PKU)-like symptoms may emerge, including more pronounced developmental abnormalities, eczema, and vomiting. Preliminary evidence indicates milder attention and organizational problems may arise when levels exceed 6 mg/dL.

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Physical

Most children have few abnormal findings on physical examination.

Some physical stigmata of PKU may be present in individuals who have phenylalanine levels near 20 mg/dL. PKU-like symptoms include eczema and fair hair and skin coloring.

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Causes

Genetic defects in phenylalanine hydroxylase cause most cases of hyperphenylalaninemia. In a few cases, defective synthesis or recycling of the biopterin cofactor is the cause (see Tetrahydrobiopterin Deficiency).

In some children with mild enzyme deficits, excessive protein intake may elevate phenylalanine levels to a range requiring treatment. The problem may resolve when protein intake is reduced to more ordinary levels. For example, infants with nonphenylketonuric hyperphenylalaninemia who consume excessive infant formula (60-70 oz/d or 1800-2100 mL/d) may demonstrate phenylalanine levels exceeding 10-12 mg/dL. Levels may fall when formula intake is restricted to 32-40 oz/d.

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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, 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

Specialty Editor Board

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

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.

Margaret M McGovern, MD, PhD  Professor and Chair of Pediatrics, Stony Brook University, New York

Margaret M McGovern, MD, PhD is a member of the following medical societies: American Academy of Pediatrics and American Society of Human Genetics

Disclosure: Genzyme Grant/research funds PI

Paul D Petry, DO, FACOP, FAAP  Consulting Staff, Freeman Pediatric Care, Freeman Health System

Paul D Petry, DO, FACOP, FAAP is a member of the following medical societies: American Academy of Osteopathy, American Academy of Pediatrics, American College of Osteopathic Pediatricians, and American Osteopathic Association

Disclosure: Nothing to disclose.

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.

References

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  2. Mak CM, Ko CH, Lam CW, Lau WL, Siu WK, Chen SP, et al. Phenylketonuria in Hong Kong Chinese: a call for hyperphenylalaninemia newborn screening in the Special Administrative Region, China. Chin Med J (Engl). Aug 2011;124(16):2556-8. [Medline].

  3. Ten Hoedt AE, Hollak CE, Boelen CC, van der Herberg-van de Wetering NA, Ter Horst NM, Jonkers CF, et al. "MY PKU": increasing self-management in patients with phenylketonuria. A randomized controlled trial. Orphanet J Rare Dis. Jun 27 2011;6:48. [Medline]. [Full Text].

  4. 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].

  5. Matalon R, Michals-Matalon K, Koch R, et al. Response of patients with phenylketonuria in the US to tetrahydrobiopterin. Mol Genet Metab. Dec 2005;86 Suppl 1:S17-21. [Medline].

  6. Sarkissian CN, Gamez A, Wang L, 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].

  7. Agostoni C, Verduci E, Massetto N, et al. Long term effects of long chain polyunsaturated fats in hyperphenylalaninemic children. Arch Dis Child. Jul 2003;88(7):582-3. [Medline].

  8. Berlin CM, Levy HL, Hanley WB. Delayed increase in blood phenylalanine concentration in phenylketonuric children initially classified as mild hyperphenylalaninemia. Screening. 1995;4:35-39.

  9. Diamond A, Prevor MB, Callender G. Prefrontal cortex cognitive deficits in children treated early and continuously for PKU. Monogr Soc Res Child Dev. 62(4):i-v, 1-208. [Medline].

  10. Fisch RO, Matalon R, Weisberg S, Michals K. Phenylketonuria: current dietary treatment practices in the United States and Canada. J Am Coll Nutr. Apr 1997;16(2):147-51. [Medline].

  11. Gassio R, Artuch R, Vilaseca MA, et al. Cognitive functions in classic phenylketonuria and mild hyperphenylalaninemia: experience in a pediatric population. Dev Med Child Neurol. 2005;47:443-8. [Medline].

  12. Medical Research Council Working Party on Phenylketonuria. Recommendations on the dietary management of phenylketonuria. Arch Dis Child. Mar 1993;68(3):426-7. [Medline].

  13. Scriver CR, Kaufman S, Eijsensmith RC. The hyperphenylalaninemias. In: The Metabolic and Molecular Bases of Inherited Disease. Vol 1. 1995:1015-76.

 
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Phenylalanine hydroxylase converts phenylalanine to tyrosine.
 
 
 
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