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Overview of phenylketonuria

Olaf A Bodamer, MD, PhD, FAAP, FACMG
Section Editor
Sihoun Hahn, MD, PhD
Deputy Editor
Elizabeth TePas, MD, MS


Phenylketonuria (PKU, MIM #261600) is a disorder affecting the aromatic amino acid, phenylalanine. It results from a deficiency of phenylalanine hydroxylase (PAH) and if untreated is characterized by intellectual disability.

An overview of PKU is presented here. A general discussion of amino acid disorders is presented separately. (See "Inborn errors of metabolism: Classification".)


The incidence of phenylketonuria (PKU) is 1 in 13,500 to 19,000 births in the United States [1]. It is less common in the African-American population, with an incidence of approximately 1 in 50,000 based on newborn screening data from the state of Maryland [2]. PKU is rare in Finland and Japan [3,4].


The hepatic enzyme, phenylalanine hydroxylase (PAH), catalyzes the conversion of the essential amino acid phenylalanine to tyrosine (figure 1). Tetrahydrobiopterin (BH4) is a cofactor required for PAH activity. This pathway accounts for most of the catabolism and is responsible for the disposal of approximately 75 percent of dietary phenylalanine, with the remainder used for protein synthesis [5]. Phenylketonuria (PKU), in most cases, is caused by deficiency of PAH [6,7]. This results in elevated blood and urine concentrations of phenylalanine and its metabolites, phenylacetate and phenyllactate. Tyrosine concentration is normal or low normal. Occasionally tyrosine concentrations are low. Defects in BH4 metabolism account for approximately 2 percent of patients with elevated phenylalanine levels. (See 'Tetrahydrobiopterin (BH4) deficiency' below.)

Complete enzyme deficiency results in classic PKU, in which serum phenylalanine concentration exceeds 20 mg/dL (1200 micromol/L). Residual enzyme activity causes moderate PKU (phenylalanine concentrations 900 to 1200 micromol/L), mild PKU (phenylalanine concentrations 600 to 900 micromol/L), mild hyperphenylalaninemia (HPA; phenylalanine concentrations 360 to 600 micromol/L), and benign mild HPA not requiring treatment (phenylalanine concentrations 120 to 360 micromol/L) [8].

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Literature review current through: Nov 2017. | This topic last updated: Jun 21, 2016.
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