Some cases of classical PKU are responsive to tetrahydrobiopterin,39,40 the co-factor for phenylalanine hydroxylase, and follow-up may also involve assessment of this response. NBS also detects babies with mildly elevated levels of phenylalanine, termed hyperphenylalaninaemia, which may be caused by rarer defects in the biosynthesis or recycling of tetrahydrobiopterin. Assessment of urine pterin levels and response to phenylalanine and tetrahydrobiopterin loads are useful in classifying these babies.