Demographic, clinical and genetic characteristics of patients with hyperphenylalaninemia followed-up in Çukurova University Department of Paediatric Metabolism and Nutrition

ABSTRACT Demographic, Clinical and Genetic Characteristics of Patients with Hyperphenylalaninemia Followed-up in Çukurova University Department of Paediatric Metabolism and Nutrition Purpose: In this study, it was aimed to evaluate the demographic, clinical and genetic characteristics of the patients who were diagnosed and followed-up in Çukurova University Deparment of Paediatric Metabolism and Nutrition with hyperphenylalaninemia Material and Method: 673 patients who were diagnosed or followed-up with hyperphenylalaninemia and whose diagnosis became definite by mutation analysis in Çukurova University Faculty of Medicine Department of Paediatric Metabolism and Nutrition between the years of 1984 and 2018 were included into this study. The data of the patients were investigated retrospectively. Their demographical characteristics, backgrounds, family history, clinical findings, laboratory data and the treatments were investigated. In addition to the patients who needed treatment, patients diagnosed as hyperphenlyalaninemia and whose blood phenyalanine levels were between 4.1 and 6 mg/dL were also examined for age appropriate IQ tests. Cranial magnetic resonance imagines were investigated. The mutation analysis was done for each patient. Their alleles were recorded separately and the allele frequencies were calculated. Results: Of 673 patients, 51.4% was female (n= 346) and 48.6% was male (n= 327). 39.5% of the patients was diagnosed as hyperphenylalaninemia (n=266), 25.9% of them was diagnosed as classic phenylketonuria (n= 174), 22.7% of them was diagnosed as moderate phenylketonuria (n= 153), and 11.9% of them was diagnosed as mild phenylketonuria (n= 80). The average blood phenylalanine levels were lower in patients who were living close to our metabolic centre. A negative relationship was found between the mothers' educational levels and the patients' blood phenylalanine levels. The IQ levels of patients who were diagnosed with newborn screening programme were higher than the IQ levels of late diagnosed patients (p=0.006). The relationship between the type of phenylketonuria and cranial magnetic resonance images was statistically important. Genetic analysis revealed homozygote mutations in 50.7% (n= 341) and compound heterozygote mutations in 42.1% of the patients (n=283). IVS10-11G>A mutation was found as the most frequent mutation with (23.7%). Than p.R261Q mutation with a frequency of 9.57% and p.A300S mutation with a frequency of 8.66% were the other important ones among 1316 alleles. Conclusion: Phenylketonuria has a heterogeneous clinic. Both the genetic and the environmental factors affect the clinic progression of phenylketonuria at different stages of disease and various degrees. Early diagnosis and initiation of protein and phenylalanine restricted diet is essential for much more improved prognosis. The IQ levels were find significantly lower in the late diagnosed patients compared with the patients who were diagnosed with newborn screening programme. There were some other factors that influence the compliance of patients to the treatment. The mothers' education levels and the distance of the family to the metabolic centre were the important factors that affect the blood phenylalanine levels in our patient group. This study was one of the largest series of phenylketonuria patients in our country, who were evaluated with genetic analysis and put forward the important factors which had affect on the prognosis of the disease. Key Words: Hyperphenylalaninemia, genotype, phenylalanine hydroxilase, phenotype.