Newborn Screening for Lysosomal Storage Disorders (Editorials‪)‬

The concept of screening newborns for inherited metabolic disorders was the brainchild of Robert Guthrie, an upstate New York microbiologist with a passion to prevent the devastating and irreversible neurologic damage sustained by victims of untreated phenylketonuria (PKU). The solution he developed was a simple and inexpensive bacterial inhibition assay for phenylalanine in blood (1). He also invented a unique method of specimen collection, in which peripheral blood was collected from a newborn's pricked heel onto a special cotton fiber filter-paper known as a "PKU card" or "Guthrie card". After the blood had dried, the specimen was mailed to a laboratory that would identify any child at risk for PKU from a concentration of phenylalanine above an age-matched control limit. Further diagnostic testing was then required to determine whether the disease was present. Treating affected children with a phenylalanine-depleted diet, started within the first month of life, was effective in preventing mental retardation. Unable to persuade the state of New York to conduct newborn screening with the test, Guthrie convinced Massachusetts that the cost of screening the entire population of newborns and treating affected children with the special diet was less than the cost to society of untreated PKU cases. Thus, in 1963 began state-mandated newborn screening for PKU (2). The test was gradually adopted by other states and eventually by countries all over the world. The success of PKU screening in dried blood spots (DBS), which identifies -200 new cases annually in the United States alone, prompted the addition of tests for other disorders that fit the PKU paradigm. By the mid1990s, most newborn screening programs were screening for only three to six metabolic disorders, and many were also screening for hemoglobinopathies. By that time, a new test based on tandem mass spectrometry (MS/MS) was shown to be effective for the identification of up to 20 disorders in several different metabolic pathways [e.g., see Refs. (3-6) from this journal]. The range of detectable disorders includes medium-chain acyl-CoA dehydrogenase deficiency (MCAD), one of several related fatty acid oxidation disorders. The basic method was developed by a team at Duke University in collaboration with the North Carolina Newborn Screening Laboratory (7). Subsequently, the method was automated (8) and brought into limited private and public service in several locations, including Australia, South America, Saudi Arabia, Bavaria, Pennsylvania, North Carolina, and New England.