Delayed increase in blood phenylalanine concentration in phenylketonuric children initially classified as mild hyperphenylalaninemia

Introduction: Confirmatory blood phenylalanine concentrations obtained after newborn screening identification are used to establish the diagnosis of phenylketonuria (PKU) or mild hyperphenylalaninemia (MHP). This diagnosis usually determines whether dietary treatment is necessary. When the phenylalanine level is in the range of MHP and diet is not given, there is a certain degree of complacency about followup beyond the first 6-12 months of age, since in MHP the levels usually remain in that range even with a normal diet. However, we have encountered infants whose blood phenylalanine levels rose very slowly from below those considered for dietary therapy to levels for which diet is advisable. Methods: Newborn screening for PKU was performed by Guthrie bacterial inhibition assay (GBIA). Followup blood phenylalanine levels were obtained in plasma by the amino acid analyzer, in serum by McCaman-Robins fluorometric assay, or in whole blood by GBIA. Results: The initial confirmatory phenylalanine levels in the four infants ranged from 3.0 to 8.4 mg/dl (180-509 μM). At ages ranging from 11 to 21 months and while on normal diets, the blood phenylalanine levels rose to a range of 16.0 to 18.5 mg/dl (970-1120 μM), and dietary treatment (in three infants) was given. Discussion: This experience emphasizes the need for frequent and consistent followup of the blood phenylalanine levels of infants classified as having MHP and not given dietary treatment. This also emphasizes the potential value of genotyping the phenylalanine hydroxylase (PAH) gene in infants to determine the category of hyperphenylalaninemia as early as possible.