Dr. Guthrie was born in Marionville, MO, in 1916. He grew up in Minnesota, where he earned his medical degree in 1942 and his PhD in bacteriology in 1946 at the University of Minnesota. For the first 12 years of Dr. Guthrie’s career, he was a principal cancer scientist at the Roswell Park Cancer Institute in Buffalo, NY. During this time, Dr. Guthrie’s second son John was born mentally handicapped (1947) and his 15-month-old niece was diagnosed with PKU (1958). By Dr. Guthrie’s own account, it was the birth of his second son John that motivated him to pursue research aimed at preventing mental retardation and developmental disabilities. It was the birth of his niece that brought to his attention the treatable causes of mental retardation.

https://academic.oup.com/labmed/article/40/12/748/2588794

Several groups of inherited metabolic disorders, most notably the organic acidemias, urea cycle defects, and certain disorders of amino acid metabolism, typically present with acute life-threatening symptoms of an encephalopathy. These symptoms are the result of toxic effects of accumulating metabolites on the central nervous system (CNS). Because most of these metabolites cross the placenta and are cleared by the mother during gestation, affected infants usually appear normal at birth. The interval between birth and onset of clinical symptoms ranges from hours to months

source= Barbara K. Burton,MD  http://www.pediatricsdigest.mobi/content/102/6/e69.full