This is a time of rapid progress in the identification of human genes, including genes in which mutations cause disease or a predisposition to it. Consequently, genetic tests are currently available for an increasing number of disorders. Many of these tests will be used only when clinical suspicion is aroused. Prompt diagnosis of genetic disease is important for two reasons. First, therapeutic interventions are now available for some genetic disorders. Early therapy may result in a better outcome for a significant number of conditions. Second, diagnosis is followed by genetic counseling, which informs parents about recurrence risk and future reproductive options.

In the first part of this section, early clinical manifestations of inherited metabolic disorders are considered and how they should be evaluated by primary care clinicians. In the second part, population-wide screening is considered—that is, testing without regard to occurrence in a family. With the advent of expanded newborn screening, infants with selected genetic-metabolic diseases will be recognized with less severe symptoms, providing a unique opportunity to reduce the early mortality and morbidity associated with these disorders. However, clinicians should not rely on newborn screening alone; practitioners will continue to suspect and diagnose metabolic disease throughout the lifetime of their patients. The outcome of newborn screening programs will highlight a wide clinical spectrum in these disorders from the severely affected to the functionally benign, educating the practitioner regarding the natural history of disease and its unforeseen complications and encouraging critical appraisal of current and novel management interventions.