Phenylketonuria (PKU) typically is diagnosed through a blood test. A newborn screening test is performed at the hospital after the baby’s birth. All 50 states require this testing, which is usually performed with a heelstick (prick in the heel) a day or two after the baby is born. Performing the test in the first 24 hours after birth may result in inaccuracies (false negatives). In addition, the test must not be performed until the child has ingested some protein. Tests are considered highly accurate as long as they are performed within seven days of birth. If the screening test is positive, further testing will be performed to positively diagnose PKU. Researchers are investigating potential new blood tests to detect PKU, including improving the accuracy of earlier tests.

In some cases, chorionic villus sampling (CVS) may be performed prior to a child’s birth to detect PKU. During this procedure, a needle is inserted into the lower belly of a pregnant woman to obtain a small sampling of cells from the placenta for analysis. 

If children are diagnosed with PKU, they will undergo treatment that involves a special diet to prevent possible brain damage. Older adults who have a history of PKU, have gone off the diet and have experienced deficits in motor function and cognitive difficulties or decline may undergo magnetic resonance imaging (MRI) testing to determine if the condition has affected the brain. MRI testing can reveal evidence of demyelination (loss of myelin, a substance in the white matter that insulates nerve endings).