Phenylketonuria (PKU) is an inborn error of metabolism that is detectable during the first days of life with appropriate blood testing (e.g., during routine neonatal screening). PKU is characterized by absence or deficiency of an enzyme (phenylalanine hydroxylase) that is responsible for processing the essential amino acid phenylalanine. (Amino acids, the chemical building blocks of proteins, are essential for proper growth and development.) With normal enzymatic activity, phenylalanine is converted to another amino acid (tyrosine), which is then utilized by the body. However, when the phenylalanine hydroxylase enzyme is absent or deficient, phenylalanine abnormally accumulates in the blood and is toxic to brain tissue.
Symptoms associated with PKU are typically absent in newborns. Affected infants may be abnormally drowsy and listless (lethargic) and have difficulties feeding. In addition, untreated infants with PKU tend to have unusually light eyes, skin, and hair (light pigmentation) and may develop a rash that appears similar to eczema, an inflammatory skin condition that may be characterized by itching, redness, and blistering in affected areas.
Without treatment, most infants with PKU develop mental retardation that is typically severe. Those with untreated PKU may also develop additional neurologic symptoms, such as episodes of uncontrolled electrical activity in the brain (seizures), abnormally increased activity (hyperactivity), poor coordination and a clumsy manner of walking (gait), abnormal posturing, aggressive behavior, or psychiatric disturbances. Additional symptoms and findings may include nausea, vomiting, and a musty or "mousy" body odor due to the presence of a by-product of phenylalanine (phenylacetic acid) in the urine and sweat.
To prevent mental retardation, treatment consists of a carefully controlled, phenylalanine-restricted diet beginning during the first days or weeks of life. Most experts suggest that a phenylalanine-restricted diet should be lifelong in persons with classical PKU. Classical PKU refers to persons with 2 severe mutations of the phenylalanine hydroxylase gene.