The importance of prenatal genetic diagnosis in prophylaxis of Phenylketonuria: clinical case

Introduction. Phenylketonuria (PKU) is an autosomal recessive genetic disorder caused by mutation in the allele genes responsible for the synthesis of phenylalanine hydroxylase (PAH) enzyme located on the 12 chromosome. The role of the phenylalanine hydroxylase enzyme is to convert the amino acid phenylalanine to the amino acid tyrosine. Thus, the disorder of the metabolism of this protein leads to excessive accumulation of phenylalanine that has toxic manifestations in the body. Loss of this enzyme results in mental retardation, organ damage, unusual posture and can lead to severely compromised pregnancy in cases of maternal PKU. Case presentation. Patient P.E. after the first pregnancy was diagnosed to bear PAH gene mutations in both alleles, found on chromosome 12. Antecedents: The first pregnancy - boy, born at 39 weeks, weight - 2800 g, walks from the age of 1 year and 2 months. Diagnosed with PKU when he was 1 year old, with the clinical signs: mental retardation, organ damage, unusual posture, elevated serum phenylalanine – 8,2 U/l. PKU diagnosis was confirmed by genetic tests: mutations in both alleles of the PAH gene, found on chromosome 12. In the 2nd pregnancy (male fetus), prenatal genetic diagnosis (PGD) through amniocentesis didn’t detect any mutation in the PAH gene. The boy was born healthy, on term. In the 3rd pregnancy (male fetus), the PGD detected the mutations in both alleles of the PAH gene, found on chromosome 12. By medical indication, the pregnancy was interrupted at 19 w.g. Currently, the woman is pregnant with her 4th pregnancy at term of 9 w.g. The mutations in the PAH gene were not detected. The pregnancy will be carried to term. Discussion. The study included one clinical case of a pregnant woman, 32 years old, investigated for abnormal PAH gene using molecular-genetic analysis (amniocentesis) in order to achieve early detection and to prevent the birth of children with PKU. Conclusion. Genetic counseling and PGD in PKU prophylaxis in risk groups for this disease are highly important. Performing PGD in women bearing the defective DG prevents the birth of children with PKU also helps to provide better treatment and management strategies for postpartum diagnosed children