Screening for Phenylketonuria

Abstract

Newborn screening for phenylketonuria (PKU) started with Robert Guthrie (1916–1995) who developed the bacterial inhibition test for the semiquantitative analysis of phenylalanine, which was the first test suitable for high throughput analysis. In addition, he introduced the ‘Guthrie filter card’ as a transport medium for dried blood which is still used today. Realizing the potential of his approach for early diagnosis and the fact that a low-phenylalanine diet prevented the neurological sequelae of untreated PKU, Robert Guthrie became the first and utmost advocate of newborn screening for PKU. Following the first PKU newborn screening program in Buffalo, N.Y., USA, in the 1960s, additional newborn screening programs were initiated around the world in the 1960s and 1970s. Newborn screening has since been recognized as an important public health measure, and most countries have ongoing newborn screening programs for PKU and other inborn errors of metabolism. Since the first programs, it has been recognized that early diagnosis of PKU and subsequent initiation of a low phenylalanine diet results in normal neurological outcomes – in contrast to the severe mental retardation in untreated PKU. Today’s newborn screening laboratories use photometric assays or tandem mass spectrometry for analysis of phenylalanine rather than the bacterial inhibition test. This has led to an increased number of cases with hyperphenylalaninemia that often do not require dietary treatment. Any elevated phenylalanine level in a neonate needs to be followed by a second specimen for repeat analysis of phenylalanine and tyrosine. Confirmation of elevated phenylalanine levels with low to normal tyrosine levels requires analysis of urine pterines and dihydropterine reductase activity in red cells to rule out an inborn error of biopterin metabolism. In any neonate whose blood phenylalanine levels exceed 6 mg/dl, a tetrahydrobiopterin loading test should be performed and dietary therapy should be initiated. The level at which dietary therapy is started may be different between the USA, UK and continental Europe.

Parental attitudes toward newborn screening for Duchenne/Becker muscular dystrophy and spinal muscular atrophy

“…Robert Guthrie developed a test for PKU using only a drop of blood that was inexpensive, fast, and accurate (Bodamer, 2010). This became the first "newborn screen" used to screen all infants while still in the hospital, in order to start a modified diet as early as possible (Wilcken, 2008).…”

“…This became the first "newborn screen" used to screen all infants while still in the hospital, in order to start a modified diet as early as possible (Wilcken, 2008). Dried blood spots are still collected on Guthrie cards made of special filter paper (Bodamer, 2010).…”

“…After the development of a reliable population screen for PKU, screens for several other diseases were created (Bodamer, 2010). In 1968, the World Health Organization commissioned a book addressing the ethical principles and practices of screening newborns (Wilson and Jungner, 1968).…”

“…Guthrie's first PKU screen was a bacterial inhibition assay (Bodamer, 2010), but this has been replaced in many states by the development of tandem mass spectrometry (MS/MS), which can screen multiple samples for multiple diseases simultaneously (Naylor, 1999). Polymerase chain reaction (PCR) is used to screen for hemoglobinopathies (Jinks, 1989).…”

„Enthält eine Phenylalaninquelle“

“… Der PKU‐Test nach Guthrie (1963) Mit dem Guthrie‐Test lässt sich eine krankhaft erhöhte Phenylalanin‐Konzentration im Blut der Neugeborenen bereits nach wenigen Tagen feststellen. Die Wachstumsringe von B. subtilis sind bei erhöhten Phenylalaninkonzentrationen auf den Agarplatten rund um die Blutproben deutlich zu erkennen (Pfeile), ein sicheres Anzeichen auf PKU . [Bildquelle: links: Armigo‐commonswiki, CC 3.0 wikimedia commons, rechts: www.pkutest.com/2012/07/22/dr‐robert‐guthrie‐father‐mass‐newborn‐screening/] …”