No abstract

ExtractExcretion in urine of o-hydroxyphenylacetic acid (0-OH-PAA) was measured quantitatively during a 24-hr period in 43 children ranging from 2 weeks to 12 years of age who were affected by different types of hyperphenylalaninemia (20 typical phenylketonuria (PKU) 7 atypical PKU, and 16 mild forms according to the classification of Auerbach et 01.); 28 out of the 33 cases diagnosed at birth in the course of a screening program were examined before reaching 3 months of age. Phenylpyruvic acid (PPA) excretion was estimated at the same time semiquantitatively.I t was found ( I ) that ferric chloride tests were negative constantly and the daily excretion of o-OH-PAA was always inferior to 5 p~/ 2 4 hr in the younger group when the level of phenylalanine in plasma was below 1.5 pmol/ml; (2) that o-OH-PAA excretion increased significantly as the children got older : 1 1.0 f 3.8 before 3 months, 16.1 f 15.9 at 6 months, 75.0 f 48.5 at 1 year, and 122.1 i 84.7 p~/ 2 4 hr at 2 years of age for levels of phenylalanine in plasma which ranged from 1.5 to 2.1 pmol/ ml; (3) that the excretion thresholds for o-OH-PAA and PPA reached adult values (0.4-0.5 and 0.7-0.9 pmol/ml, respectively) only after 2 years.In 16 cases, using intravenous perfusion of 0.06 M L-phenylalanine, we have shown also that the PPA and o-OH-PAA excretion was identical whatever the type of (PKU) or mild forms) insofar as the levels of phenylalanine in plasma reached (1.5-3.0 pmol/ml) were equal in both types. Speculation This paper presents observations which demonstrate that only a minute amount of o-OH-PAA is excreted daily in the urine of both classic PKU and other forms of hyperphenylalaninemia during the first months of life. I t is suggested that this very low excretion is caused by a delayed maturation of phenylalanine transaminase; it is further proposed that the different types of hyperphenylalaninemia, with the exception of those caused by a deficiency of the tyrosine-oxidizing system, are all secondary to mutations affecting the phenylalanine hydrox>lase system.