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1. Background
Phenylketonuria, an inborn error of metabolism (PKU; OMIM 261600), is mainly considered in the context of neurological complications resulting from accumulation of phenylalanine and its metabolites. However, the essence of the disease is impairment of phenylalanine hydroxylase (PAH) activity in the liver, first observed by Jervis in 1953, which results in blocking of the conversion of phenylalanine to tyrosine (1-4). The treatment-compliance of PKU patients results in a normal life expectancy with health problems similar to that of the normal population and frequency of drug use. These factors tend to stress the liver’s ability to metabolize xenobiotics. Although the activity of PAH, a cytosolic enzyme, was already assessed (5), the microsomal function of the liver, necessary for the metabolism of xenobiotics, has never been studied. The liver system engaged in the metabolism of drugs is the cytochrome P450 family (6).
The 13C-methacetin breath test (13C-MBT) is a non-invasive, easy to perform and safe method used for the evaluation of microsomal liver function (7). Methacetin undergoes O-dealkylation by cytochrome P450 1A2 (CYP1A2) to acetaminophen and 13CO2 (8). 13CO2 output in exhaled air reflects the activity of cytochrome P450 enzymes and thereby microsomal function of the liver (9). The available data of previous studies show that 13C-MBT was used for the assessment of liver status in such conditions as hepatitis B and C (10), non-alcoholic steatohepatitis (11), fibrosis (12, 13) and cirrhosis (13, 14).
The aim of this study was to assess the microsomal liver function in PKU patients by 13C-MBT.
2. Methods 2.1. Study Design
The study group comprised of 20 subjects (13 females and 7 males) aged 15 - 34 years with classical PKU from the department of pediatric gastroenterology and metabolic diseases, medical university, Poznan and the Voivodeship hospital, Wroclaw, Poland.
Inclusion criteria were defined as: the diagnosis of classical PKU based on the result of national newborn screening and confirmed by molecular tests (15, 16), aged 15 years or older, and willingness to participate in the study. Exclusion criteria were: non-classical forms of PKU (mild PKU, maternal PKU, mild hyperphenylalaninemia, BH4 deficiency) and pregnancy. For analysis, the PKU patients were additionally divided into the group with recommended Phe levels (< 10 mg/dL) and the group with high Phe levels (> 10...