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

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 mo nth period (n = 404 381). Methods-Dried blood spot specimens were analysed at nine laboratories. To a ssure that the results reported from multiple sites were matched accurately , an automated methodology was chosen that included sample processing, anal ysis, telecommunications, reporting, and information technology. Phenylalan ine and tyrosine concentrations were measured independently by continuous f low fluorometry, for which precision, recovery, detection Limits, carryover , chemical specificity, reportable range, and number of repeats are reporte d. Results-In this study, 37% of the newborns were tested at less than 24 hour s of age. For this population, using a phenylalanine only cut off of 200 mu mol/l, there were 48 recalled infants per case of classic PKU. Using the p henylalanine:tyrosine ratio with a cut off of 1.50, screen positives could be reported with phenylalanine as low as 150 mu mol/l and with only 12 reca lls per case. Conclusions-The phenylalanine:tyrosine ratio can be measured accurately at multiple laboratories using two channel chemical analyses. Having applied t he methods to the routine clinical screening of a large population, it was confirmed that the clinical sensitivity and specificity of the PKU screenin g test are higher when the phenylalanine:tyrosine ratio is incorporated int o the cut off than when the cut off is based on the phenylalanine concentra tion alone.