Identified PAH V230A and PAH V230I mutations in a family with diverse clinical presentations

Abstract

Key Clinical Message 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. Additionally, some patients with mild hyperphenylalaninemia (mHPA), who has serum phenylalanine levels <360 μmol/L, do not require treatment. 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. In this study, we report an asymptomatic adult with mHPA who had never taken any medical intervention to control or lower her serum phenylalanine level (Phe). She had 179 μmol/L serum phenylalanine level and carried p.[V230A];[V230I] genotype. Her child was affected with phenylketonuria and had p.[V230A];[V230A] genotype. Both pathogenic variants detected in the asymptomatic adult with mHPA were computationally analyzed to assess their pathogenicity and the p.V230I pathogenic variant was demonstrated to be responsible for the mHPA phenotype in the asymptomatic adult detected in this study. The findings in this study could contribute to genetic counseling and treatment for families and individuals with p.[V2030I];[V230A] genotype.

Keywords

• endocrinology and metabolic disorders
• genetics and genomics
• health informatics
• pathology and laboratory medicine
• pediatrics and adolescent medicine