Highlights & Basics
- Phenylketonuria (PKU) is a rare inborn error of metabolism associated with elevated blood phenylalanine. Clinical features in the untreated patient include intellectual disability, seizures, and eczema.
- Early treated patients typically have normal intellectual development with an IQ within the normal range, although subtle neurocognitive deficits are observed and there is an increased incidence of attention deficit disorder, executive functioning deficits, and mental health concerns.
- Caused by a deficiency of hepatic phenylalanine hydroxylase activity. Gene mutations are biallelic, most often compound heterozygous, and therefore residual enzyme activity and blood phenylalanine levels are variable and correlate with the severity of the disorder.
- Diagnosed by newborn screening and managed by a multidisciplinary team of specialists.
- Treatment for most patients involves restriction of dietary protein and phenylalanine, and supplementation with phenylalanine-free amino acid mixtures. Tetrahydrobiopterin (BH4)-responsive patients may also be treated with sapropterin. Pegvaliase is a newer option that can allow for a regular diet.
Quick Reference
History & Exam
Key Factors
Other Factors
Diagnostics Tests
Treatment Options
Definition
Epidemiology
Etiology
Pathophysiology
Citations
National Institutes of Health Consensus Development Panel. National Institutes of Health consensus development conference statement: phenylketonuria - screening and management. 2000 [internet publication].[Full Text]
Mitchell JJ, Scriver CR. Phenylalanine hydroxylase deficiency. In: Pagon RA, Bird TC, Dolan CR, et al, eds. GeneReviews [Internet]. Seattle, WA: University of Washington, Seattle; 1993-2000.[Abstract][Full Text]
Scriver CR, Kaufman S. The hyperphenylalaninemias: phenylalanine hydroxylase deficiency. In: Scriver CR, Beaudet AL, Sly SW, et al, eds; Childs B, Kinzler KW, Vogelstein B, assoc eds. The metabolic and molecular bases of inherited disease. 8th ed. New York, NY: McGraw-Hill; 2001:1667-1724.
1. National Institutes of Health Consensus Development Panel. National Institutes of Health consensus development conference statement: phenylketonuria - screening and management. 2000 [internet publication].[Full Text]
2. Mitchell JJ, Scriver CR. Phenylalanine hydroxylase deficiency. In: Pagon RA, Bird TC, Dolan CR, et al, eds. GeneReviews [Internet]. Seattle, WA: University of Washington, Seattle; 1993-2000.[Abstract][Full Text]
3. Scriver CR, Kaufman S. The hyperphenylalaninemias: phenylalanine hydroxylase deficiency. In: Scriver CR, Beaudet AL, Sly SW, et al, eds; Childs B, Kinzler KW, Vogelstein B, assoc eds. The metabolic and molecular bases of inherited disease. 8th ed. New York, NY: McGraw-Hill; 2001:1667-1724.
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