Jw. Eastman et al., Use of the phenylalanine : tyrosine ratio to test newborns for phenylketonuria in a large public health screening programme, J MED SCREE, 7(3), 2000, pp. 131-135
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.