Çağrı DOĞAN, Elif DOĞAN
Middle Black Sea Journal of Health Science - 2026;12(2):353-359
Background: Phenylketonuria (PKU) is an autosomal recessive metabolic disorder caused by deficient phenylalanine hydroxylase (PAH) enzyme activity. The present study aims to elucidate the genetic and molecular complexity of a family with previously diagnosed PKU, emphasising the importance of genetic screening and diagnostic testing in the management of inherited metabolic disorders. Case Report: Following the initial biochemical diagnosis via newborn screening, a four-membered family (mother and three daughters from two different marriages) underwent molecular genetic testing. DNA was extracted, and Next Generation Sequencing (NGS) was performed to analyse mutations in the PAH gene. Three daughters were evaluated: two were diagnosed with PKU and one was identified as a carrier. All affected individuals were compound heterozygotes with pathogenic variants in the PAH gene. The identified mutations were PAH (NM_000277.3): c.1208C> T (p.A403V), PAH (NM_000277.3): c.1243G>A (p.D415N) and PAH (NM_000277.3): c.688G>A (p.V230I), all previously reported in the literature as pathogenic with mild to moderate phenotypic effects. One daughter exhibited normal development and was a heterozygous carrier. Despite delayed dietary compliance in the affected individuals, neurodevelopmental impairments were moderate, likely reflecting genotype -phenotype correlations. Conclusion: Inherited metabolic diseases like PKU impose significant but preventable burdens on individuals and health systems. Pre -marital genetic counselling and targeted carrier screening, especially in populations with high consanguinity rates, are vital tools for prevention. Strengthening public awareness and genetic literacy can help cultivate a healthier generation through informed reproductive choices.
