Phenylketonuria (PKU), rare hereditary disease in newborns in which the enzyme that processes the amino acid phenylalanine is defective or missing, leading to the accumulation of phenylalanine in an affected child’s blood shortly after birth. If not treated within the first few weeks of life, PKU can cause mental retardation and other serious neurological problems. PKU affects about one in every 10,000 to 12,000 babies born in the United States. When a strict diet that limits phenylalanine is begun early and is carefully maintained, affected children can develop normally.
Phenylalanine is normally converted to tyrosine, another amino acid. The enzyme that triggers this conversion, called phenylalanine hydroxylase, does not work properly in PKU patients. As a result, excess phenylalanine builds up in the blood, damaging an infant's developing central nervous system. This can eventually cause mental retardation, seizures, tremors, behavioral disorders, and some forms of mental illness. Untreated persons with PKU commonly have blond hair and blue eyes because excess phenylalanine inhibits the formation of melanin, the pigment that gives hair and eyes their color.
PKU is an autosomal recessive genetic disorder—that is, a child must inherit a defective gene from both parents. Several hundred forms of the defective gene are known to cause PKU. Some of them cause classical PKU, where the blood phenylalanine level is very high at birth and the risk of mental retardation and other problems is great. Other mutations cause less severe forms of the disease. Approximately one out of every 50 people in the United States population carries a single defective PKU gene. This single defective gene has no adverse effects on people who carry it, but if two carriers conceive a child, there is a one in four chance that the baby will inherit two defective genes and be born with PKU.
Newborn babies with PKU typically do not show signs of the disease until weeks or months after birth. In the early 1960s, American medical researcher Robert Guthrie developed a test to diagnose PKU in newborns. The Guthrie test or one of several more recently developed diagnostic tests measure the concentration of phenylalanine in a newborn’s blood. PKU testing is now mandatory for all newborn babies in the United States before they leave the hospital.
It is crucial that babies diagnosed with PKU begin a diet low in phenylalanine within the first weeks of life. Foods that contain protein also contain phenylalanine; for this reason, people with PKU must avoid all concentrated sources of protein, including meat, fish, poultry, milk, eggs, dairy products, nuts and legumes, and even many products containing regular flour. Because babies need a variety of nutrients to develop and grow, a special phenylalanine-free formula high in protein is used as a nutritional substitute. Older children and teenagers with PKU continue drinking the formula, supplementing their diets with a variety of low protein foods, such as fruits, vegetables, some grains, and special low-protein products.
Doctors formerly believed that children with PKU could be safely taken off the special diet by early school age. But it is now recognized that stopping the diet may lead to a variety of serious problems, including learning disabilities, behavior problems, neurological abnormalities, and mental illness. Most experts now recommend that people with PKU continue the diet for life. Experts are also finding that even mentally retarded adults with PKU, who were born before newborn screening was established, experience reductions in PKU-related symptoms when following a diet low in phenylalanine. Adults can show improvements in areas such as concentration, communication, and behavioral problems. In the United States, specialized PKU treatment programs in each state help patients manage and monitor the diet. Research is ongoing to find other alternatives to the difficult diet for PKU treatment.
Pregnant women with PKU have an especially important need to keep their blood phenylalanine levels low. In maternal PKU syndrome, high phenylalanine levels in the mother can cause serious problems for the baby, including low birth weight, small head size, heart defects, and mental retardation, even if the baby does not have PKU. This disorder can be prevented if the woman is on the special diet before conception and maintains low blood phenylalanine levels throughout pregnancy.