Hyperphenylalaninemia Treatment & Management
- Author: Georgianne L Arnold, MD; Chief Editor: Bruce Buehler, MD more...
Medical Care
If available, patients should be evaluated at a phenylketonuria (PKU) treatment center. The extent of the hyperphenylalaninemia determines the nature and frequency of follow-up.[3]
In one study, 54% of patients with phenylalanine levels less than 600 mmol (10 mg/dL) demonstrated a decline of 30% or more in plasma phenylalanine levels when sapropterin (commercial tetrahydrobiopterin cofactor) was administered at a dose of 10 mg/kg/d.[4] The percentage of patients who responded declined with increasing plasma phenylalanine levels. Response to sapropterin may improve at a dose of 20 mg/kg/d.[5]
Animal studies are underway for injectable phenylamine ammonium lyase, an enzyme substitute. This shows promise as an alternative treatment to control phenylalanine levels.[6]
Consultations
If dietary treatment is necessary, refer the patient to a dietitian experienced with PKU (usually a member of a PKU treatment team).
Refer families of affected infants to a medical geneticist or genetic counselor to review the inheritance of hyperphenylalaninemia.
Diet
Determine the degree of dietary phenylalanine restriction for each patient based on untreated phenylalanine levels. For more detailed information on a phenylalanine-restricted diet, see Phenylketonuria.
Breastfeeding is usually possible and should not be stopped unless instructed by a local health official or treatment center.
Aspartame restriction may be indicated. Phenylalanine is a primary component of aspartame.
Aspartame may be present in many artificially sweetened substances, including medicines, vitamins, beverages, and foods. A pharmacist can help determine if a medication has a significant amount of aspartame.
The amount of aspartame in a children's vitamin or in a teaspoon of antibiotic may be significant for a child who can tolerate only 200 mg/d of phenylalanine, yet such a dose may be insignificant for a child who can tolerate more than 1000 mg/d.
Stringent phenylalanine-restricted diets have been reported to cause deficiencies of zinc, selenium, and other nutrients in patients with PKU. However, the most common deficiency is mild-to-moderate iron deficiency. Although iron is supplemented in the amino acid supplement formulas consumed by patients as part of such diets, absence of dietary heme iron and poor absorption of supplemental iron often result in deficiency.
Prick BW, Hop WC, Duvekot JJ. Maternal phenylketonuria and hyperphenylalaninemia in pregnancy: pregnancy complications and neonatal sequelae in untreated and treated pregnancies. Am J Clin Nutr. Feb 2012;95(2):374-82. [Medline].
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].
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].
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].
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].
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].
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].
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.
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].
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].
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].
Medical Research Council Working Party on Phenylketonuria. Recommendations on the dietary management of phenylketonuria. Arch Dis Child. Mar 1993;68(3):426-7. [Medline].
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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