The importance of the evaluation of the phenylalanine tolerance in phenylketonuria

Objective: In the follow-up of hyperphenylalaninemia (HPA) cases (phenylalanine≥120 µmol / L), because of the inconsistency between the predicted phenotype in the literature and the clinical phenotype and phenalanine (Phe) tolerance is the most important parameter in phenotyping; it was aimed to determine the value of phenylalanine tolerance in the patient group with certain disease-causing mutation (p.L48S) and to determine the value of their use in monitoring phenylketonuria (PKU) cases. Material and Method: In this cross-sectional study, 65 PKU patients who are carrying a specific mutation (p.L48S) were compared. The data of the patients were evaluated and the data about the demographic and first diagnostic features and lifelong Phe tolerances after one year were evaluated. The current status of the patients was evaluated and the body weight and height, Phe restricted tyrosine (Tyr)-rich nutritional therapy application was learned, current three-day (two weekdays, one weekend) food consumption records (FCRs) were obtained. Current three-day FCRs are analysed with single 7.2 version of the BeBİS (Nutrition Information System) program by the dietician (M.M.) and the amount of protein (g/day), carbohydrate (g/day), fat (g/day), calories (kcal/day) and Phe (mg/day) was calculated. The amount of protein taken were evaluated separately for natural protein and Phe-free medical L-amino acid formula. Samples for morning fasting blood Phe-Tyr values ​​were taken at the last hour of FCR reception. Phe tolerances (mg/day and mg/kg/day) obtained from natural protein were determined in patients who had quantitative Phe levels at age appropriate limits during nutritional therapy. Results: When the first clinical phenotypes of cases were examined, all three PKU phenotypes (Mild HPA 16.9% Mild PKU (n=11), 40% (n=26), Classic PKU 43% (n=28)) were determined. Initial diagnosis Mild HPA can be passed to Mild PKU, at the age of mean±SD 11.65±7.43 months, by exceeding phenylalanine level to ≥600 μmol / L in the follow-up, it was found that this rate was higher [n =8(72%)] in this study. After ≥2 years of age homozygous cases' Phe tolerance (mg/day, mg/kg/day) is higher when compared to heterozygote cases of p.L48S at different ages. Life-long Phe tolerance (mg/day, mg/kg/day) before the age of <7 years, there was no significant difference between the cases with Mild PKU and Classic PKU clinical phenotype at different ages. After the age of 7, Phe tolerance (mg/day, mg/kg/day) decreased, and of cases with Mild PKU clinical phenotype was found to be higher than Phe tolerance (mg/day, mg/kg/day) of cases with Classic PKU clinical phenotype (p=0,026, p=0,047). Phe tolerance (mg/kg/day) of current three days food consumption record analysis and lifetime Phe tolerance (mg/kg/day) in patents older than 7 years are found significantly correlated; but there was no correlation between the Phe tolerances (mg/kg/day) when compared with the patients younger than 7 years of age (p=0,001, p>0,05). Conclusion: The study shows that while specifying PKU patients' real clinical phenotype, evaluating with monitoring Phe tolerance is more significant than first diagnosis quantitative Phe levels (p=0,001). Moreover, specification of Phe tolerance is essential in lifetime nutrition treatment. Therefore, it is stressed that PKU patients should be monitored individually in each case.