Receiver operating characteristic plots to evaluate Guthrie, Wallac, and Isolab phenylalanine kit performance for newborn phenylketonuria screening

We used ROC plots to evaluate the clinical performance of the Guthrie, Wallac, and Isolab assays for newborn phenylketonuria (PKU) screening and assessed the screening discriminatory power of these three assays by the area under the ROC plot, Youden’s J index, and the likelihood ratio. The use of these plots not only allows us to pinpoint the exact cutoff value in screening, but also provides a direct comparison of these three different assays in clinical outcome performance. The optimum cutoff for the newborn PKU screening is a blood phenylalanine concentration of 0.30, 0.27, and 0.18 mmol/L for the Guthrie, Wallac, and Isolab assays, respectively. We conclude that the Wallac and Isolab kits, like the Guthrie assay, are suitable for newborn PKU screening.

Neonatal Screening for Phenylketonuria: II. Age Dependence of Initial Phenylalanine in Infants With PKU

The relationships between initial and follow-up blood phenylalanine concentration and between initial concentration and age were examined in infants with elevated screening tests. Data were provided by health departments and phenylketonuria (PKU) clinics. Among infants who attained levels of 20 mg/100 ml or more the following was observed: (1) one-fourth had only minimal elevations (to less than 10 mg/100 ml) on the initial screening test; (2) of those with minimal elevations 66% were screened on or before the third day of life; (3) most of those whose initial elevations were more than minimally elevated and most of those with minimal elevations who were screened early had follow-up phenylalanines of 30 mg/100 ml or more. In contrast, those with minimal initial elevations who were screened late were more likely to have follow-up phenylalanines between 20 and 30 mg/100 ml. They may represent a different form of PKU. The findings suggest that as long as most infants in the United States continue to be screened on or before 4 days of age, some infants with PKU will be missed.