Investigation of oxidative parameters in classical phenylketonuric patients

Phenylketonuria (PKU) is the most frequent inherited disorder of amino acid metabolism. PKU is caused by deficiency of phenylalanine-4- hydroxylase (PAH), which is a liver-specific enzyme that catalyzes the conversion of l-phenylalanine (Phe) to l-tyrosine (Tyr). Failure of this conversion results in elevated concentrations of Phe and its metabolites. Phenylketonuric patients present as the major clinical feature mental retardation, whose pathomechanisms are poorly understood. In recent years, mounting evidence has emerged indicating that oxidative stress is possibly involved in the pathology of PKU. In this work, we aimed a large spectrum of oxidative stress parameters including Total antioxidant status (TAS), Total oxidant status (TOS), Oxidative stress index (OSI), Glutathione peroxidase (GSHPx), Paraoxonase (PON1), Coenzyme Q10 (CoQ10) and L-carnitine in serum and erythrocytes from PKU patients. The study population consisted of classical PKU patients (n=40) who were divided into two groups: early diagnosed patients (n=20) and late diagnosed patients (n=20). Early diagnosed patients were classified into two groups according to their mean Phe level: good compliance (n=10) and bad compliance (n=10). Age-matched healthy children (n=10) were used as the control group. No significant differences between early diagnosed patients and controls were observed in the levels of TAS, TOS, OSI and PON1. Glutathione peroxidase and L-carnitine levels were significantly reduced in bad compliance patients as compared to good compliance patients and controls. Late diagnosed patients were classified into two groups according to amino acid supplementation type: "received amino acid mixture" (n=10) and "received LNAA supplementation" (n=10). Age-matched healthy children (n=10) were used as the control group. No significant differences between late diagnosed patients and controls were observed TAS, TOS, OSI, PON1 and L-carnitine. GSHPx level was significantly reduced in received LNAA supplementation patients as compared to controls. Coenzyme Q10 levels was significantly reduced in received amino acid mixture patients as compared to received LNAA supplementation patients and controls. As a result, in this work when we look at the early diagnosed patients, poorly controlled patients are prone to oxidative stress. When we look at the late diagnosed patients, LNAA supplementation reduce oxidative stress compared to received amino acid mixture patients. Key words: Diet therapy, LNAA, Oxidative stress, Phenylalanine, Phenylketonuria