Phenylketonuria is an inborn error of metabolism characterized by high levels of the amino acid phenylalanine [Phe] in the blood of newborns. PKU is diagnosed by means of various versions of the Guthrie Test, first devised by Dr Robert Guthrie (1916 - 1995) after the birth of his child with PKU. In the original test, a small drop of blood taken from the heel of a newborn (left) was applied to a filter-paper disc [right]. A punch-out of the dried disc was incubated on a Petri dish plated with bacteria (Bacillus subtilis), in the presence of a growth inhibitor, B-2-thienyl-alanine. High levels of Phe in the blood sample overcame the inhibition, and allowed bacterial growth in the area around the disc. The original test has been supplanted by direct mass-spectroscopy measurement of Phe concentration in the blood sample. Conceptions at risk for PKU may also be screened by prenatal PCR-based DNA tests for the PKU-related alleles themselves.

    If an elevated level of Phe is detected, the child is placed on a phenylalanine-restricted diet for their first several years (< 10 years). This can completely offset the expected neurological effects (below). The Guthrie Test was the first widely-used peri-natal biochemical diagnostic test. Since its introduction in the early 1960s, it been used in >90% of North American hospitals, and in most other countries. Guthrie's method has been extended to many other conditions.

    Current evidence suggests that high levels of [Phe] may impair mental performance later in life, and that a Phe-restricted diet should be maintained throughout life.