Use of the phenylalanine:tyrosine ratio to test newborns for phenylketonuria in a large public health screening programme

Abstract

Objective To assess the benefits of using the phenylalanine:tyrosine ratio to screen newborns for phenylketonuria (PKU). Setting Data were collected from all newborns in California during a ten month period (n = 404 381). Methods Dried blood spot specimens were analysed at nine laboratories. To assure that the results reported from multiple sites were matched accurately, an automated methodology was chosen that included sample processing, analysis, telecommunications, reporting, and information technology. Phenylalanine and tyrosine concentrations were measured independently by continuous flow fluorometry, for which precision, recovery, detection limits, carryover, chemical specificity, reportable range, and number of repeats are reported. Results In this study, 37% of the newborns were tested at less than 24 hours of age. For this population, using a phenylalanine only cut off of 200 μmol/l, there were 48 recalled infants per case of classic PKU. Using the phenylalanine:tyrosine ratio with a cut off of 1.50, screen positives could be reported with phenylalanine as low as 150 μmol/l and with only 12 recalls per case. Conclusions The phenylalanine:tyrosine ratio can be measured accurately at multiple laboratories using two channel chemical analyses. Having applied the methods to the routine clinical screening of a large population, it was confirmed that the clinical sensitivity and specificity of the PKU screening test are higher when the phenylalanine:tyrosine ratio is incorporated into the cut off than when the cut off is based on the phenylalanine concentration alone.