Microsomal Liver Function in Patients with Phenylketonuria Assessed by 13C-Methacetin Breath Test

Abstract

Background: Although the activity of the cytosolic hepatic enzyme phenylalanine hydroxylase is impaired in phenylketonuria (PKU), the microsomal function, necessary for the metabolism of xenobiotics, has never been assessed. The aim of the study was to assess the microsomal liver function in PKU patients by 13C-methacetin breath test (13C-MBT), which measures cytochrome P450 activity. Methods: Twenty patients with classical PKU, aged 15 - 34 years, were enrolled in the study. The control group comprised of 20 healthy subjects matched for age and sex. The 13C-MBT was performed in every subject at rest after an overnight fast. Results: The values of cumulative percentage dose recovery at 120 minutes of the test (CPDR median ) were significantly lower in the PKU group than in the control group (25.1 vs 32.8 ; P = 0.0067). The lower values of the maximum momentary 13C recovery (Dmax) were observed in the PKU group than in the control group (26.6 vs. 32.1 ; P = 0.0227). The values of time to reach Dmax (Tmax) did not differ (20 vs. 20 ; P = 0.8410). The values of CPDR, Dmax and Tmax were not different between the group with abnormal (> 10 mg/dL) and normal (< 10 mg/dL) Phe level (P = 0.2799; 0.7959; 0.4812, respectively). Conclusions: The present study demonstrates that the cytochrome P450 activity in PKU patients may be reduced. However, further research is required, particularly in regards to the effect that patient diet compliance has on the microsomal liver function.