Investigation of patients with phenylketonuria followed in Akdeniz University Pediatric Metabolism Outpatient Clinic in terms of obesity and insulin resistance

Phenylketonuria (PKU); It is an autosomal recessive metabolic disease that occurs as a result of mutation in the phenylalanine hydroxylase (PAH) gene. The basis of the treatment is a phenylalanine-restricted diet. The aim of the follow-up is to prevent neurological sequelae by maintaining the blood phe levels in a therapeutic target range while maintaining the nutritional requirements to achieve normal growth and body composition. Diet compliance is good as parents control their food intake. As children grow up, meals must be carefully planned and since children cannot choose foods that are routinely consumed by their peers, dietary compliance becomes increasingly difficult. It has been observed in studies that patients' adherence to diet decreases and phe concentrations increase, especially towards adolescence. At the same time, as a result of the restriction of protein in the diet, the tendency to consume foods rich in carbohydrates and lipids increases. Despite the risks associated with high carbohydrate intake, carbohydrate metabolism is impaired in patients with PKU. Very little research has been done on it. In our study, we aimed to investigate the relationship between obesity and insulin resistance frequency in patients with phenylketonuria followed up in Akdeniz University Pediatric Metabolism Polyclinic and factors that may increase this frequency. Patients aged 3-25 years, followed up between October 2020 and February 2022, were included in the study. A total of 103 patient data were evaluated. Patients were measured at the time of diagnosis. classified according to blood phe levels. 48.5% of the patients were female and 51.5% were male. 32% of the patients were classical PKU, 9.7% moderate PKU, 33.1% mild PKU and 25.2% benign hyperphenylalanine. 77.7% of the patients were on a diet and 22.3% were being followed without a diet. 9 of 103 patients (8.7%) were using saptopterin. 4 of these 9 patients were on no diet and 5 were on a diet was being followed. According to the mean of the last three phe, 45 (43.7%) patients were poorly controlled and 58 (56.3%) well-controlled. Weight measurement values were statistically higher in the poorly controlled group (p=0.049). Insulin resistance (40%) was observed more frequently in the poorly controlled group than in the well-controlled group (19%) (p=0.019). HDL-C values were significantly lower in poorly controlled patients (p=0.001). The rate of classical PKU (46.7% and 20.7%) in the poorly controlled group and the rate of benign HPA (43.1% and 2.2%) in the well-controlled group were statistically higher (p<0.001). Insulin and HOMA-IR values were statistically higher in the pubertal group (p=0.017 and p=0.015). The median TSH value was found to be higher in the prepubertal group (p=0.001). BMI (p=0.048) values were found to be significantly higher in the moderate PKU group than in the benign HPA group. Insulin values of the benign HPA group were lower than the patients in the classical PKU and moderate PKU groups (p=0.042). In conclusion, our data provide preliminary evidence suggesting that poor adherence to a low phe diet may be associated with the risk of overweight and insulin resistance. Although studies on the follow-up and treatment process of the disease are promising, new studies are needed. Keywords: Phenylketonuria, PKU, Obesty, İnsulin Resistance, Diet