The diagnosis of phenylketonuria: a commentary.

Abstract

FOR many years after its recognition as a metabolic disorder, phenylketonuria (PKU) seemed a simple genetic defect, and the diagnosis, based on elevated levels of serum phenylalanine (or hyperphenylalaninemia) and urinary excretion of phenylpyruvic acid, equally simple. Patients were sought and found in institutions for mentally retarded. As interest in the condition grew, rare individuals with normal or borderline intelligence were identified, usually because of odd behavior. Most frequently, these individuals had lower phenylalanine levels than retarded patients. The concept arose of classic PKU, associated with severe mental retardation if untreated, and variant or atypical PKU, associated with a lesser degree of mental disability. Only when mass screening of newborn infants for PKU became widespread was the spectrum of the biochemical defect fully appreciated. It soon became apparent that not all infants with hyperphenylalaninemia had PKU. The major cause of elevated phenylalanine levels in infants was the association with