• The p[V230A]; [V230I] genotype was detected in a 32 years old normal adult with untreated mild hyperphenylalaninemia
  • Faeze Khaghani,1 Tayebeh Hamzehloei,2,*
    1. Mashhad University of medical sciences, Genetics department, Mashhad-Iran.
    2. Mashhad University of medical science, Pediatrics department. Mashhad-Iran.


  • Introduction: Phenylketonuria (PKU) is a hereditary disorder caused by phenylalanine hydroxylase enzyme (PAH) defects that might cause severe brain damage. The current main treatment, dietary management, can prevent the symptoms if commenced early. However, it has side effects if used for a long time. According to recent guidelines, treatment is not required for patients with mild hyperphenylalaninemia (mHPA) and Phenylalanine level <360 µmol/l. Since the correlation between genotype and metabolic phenotype has been demonstrated earlier, genotype-based detection of patients who do not need treatment might help with genetic counseling and choosing the most appropriate treatment option.
  • Methods: Genetic analysis was conducted for a family containing a child suffering from PKU and her parents. The level of serum Phenylalanine was assessed in subjects who carried two pathogenic variants within the PAH gene. Both of pathogenic variants detected in the normal adult with untreated mHPA were computationally analyzed to assess their pathogenicity.
  • Results: The affected child and her mother were bearing p.[V230A];[V230A] and p.[V230A];[V230I] genotypes respectively. The mother had 179 μmol/l serum Phenylalanine level, so she was a normal adult with untreated mHPA who had never taken any medical intervention to control or lower her serum Phenylalanine level. Both detected variants were pathogenic and affected the catalytic domain of the PAH enzyme diversely
  • Conclusion: The p. V230I pathogenic variant was demonstrated to be responsible for the mHPA phenotype in the normal untreated adult detected in this study.
  • Keywords: Normal adult, PAH, untreated mHPA, Phenylalanine, genotype