Measurement of hepatic phenylalanine metabolism in children using the [13C]-phenylalanine breath test and gas chromatography–mass spectrometry

The essential amino acid, phenylalanine (PA), is known to be metabolized mainly in the liver of human adults. Because the liver is still in the developmental phase, the PA-related metabolic events in infants remain unsolved. In this study, evaluations of development in hepatic PA metabolism in 37 children and 16 adults were attempted using the 13C-PA breath test (PBT). The subjects were categorized into four groups according to their ages in years and months: 2 years and 0 month to 3 years and 5 months (group I; n=12); 3 years and 6 months to 4 years and 11 months (group II, n=12); 5 years and 0 month to 6 years and 11 months (group III, n=13); and healthy adults (group IV; n=16). Changes in CO2 level of exhaled gas at various time intervals after oral administration of 13C-PA were monitored using gas chromatography–mass spectrometry to derive the 13C excretion rate, cumulative excretion curve and time maximum 13C excretion rate (TMAX). In the present investigation involving children, significant increases of maximum 13C excretion rate and cumulative excretion at 120 min after administration were established in group III. Furthermore, differences in PBT were not established between groups III and IV. The index for first-pass effect, TMAX, did not change with time. From the above findings, the 13C excretion rate increased with time although hepatic PA metabolism in infants remained underdeveloped, and children at the age of 5–7 years manifested PA metabolism similar to that of adults.