TECHNIQUES AND EFFICACY OF SCREENING

Abstract

The story of newborn screening for inborn errors of metabolism begins with the ideas expressed by Archibald Garrod in 1902. He published a paper called "The Incidence of Alkaptonuria, A Study in Chemical Individuality," in which he showed insight into the inheritance of specific chemical defects in metabolism. This was before any knowledge of enzymes or metabolism existed and was soon after the discovery of Mendel's laws of inheritance. The application of Mendel's laws of inheritance in the human organism was pioneered by Garrod. He originated the phrase "inborn errors of metabolism" that is still used today. Forty years later, Beedle and Tatum performed their Nobel prize-winning work with the mold Neurospora to demonstrate the "one gene-one enzyme" hypothesis. One of their associates, the late Dr David Bonner, later published a series of papers concerning the case of one auxotroph of Neurospora with two amino acid requirements for isoleucine and valine. This double requirement was found to be due to "internal inhibition": the accumulation of the precursor to one branch-chained amino acid, isoleucine, blocked the conversion of another branch-chained precursor to its amino acid, valine. This phenomenon of "internal inhibition" demonstrated in Neurospora was a prelude to more recent insight into human errors of metabolism, such as phenylketonuria (PKU). Bickel's publication in 1953 of a dietary treatment for PKU led to a great deal of interest in early treatment of PKU. There were many attempts to set up urine screening programs using the ferric chloride reagent that Folling used in discovering the disease in 1934.