Coexistence of phenylketonuria and tyrosinemia type 3: challenges in the dietary management.

Abstract

Objectives: Phenylketonuria (PKU) and tyrosinemia type 3 (HT3) are both rare autosomal recessive disorders of phenylalanine-tyrosine metabolism. PKU is caused by a deficiency in phenylalanine hydroxylase (PAH), leading to elevated phenylalanine (Phe) and reduced tyrosine (Tyr) levels. HT3, the rarest form of tyrosinemia, is due to a deficiency in 4-hydroxyphenylpyruvate dioxygenase (HPD).

Case presentation: We report a 5-year-old girl diagnosed with both PKU and HT3. She presented with elevated Phe levels in neonatal screening, and subsequent biochemical tests revealed both hyperphenylalaninemia and elevated Tyr levels. Genetic analysis confirmed the diagnoses, identifying homozygous mutations in both the PAH and HPD genes. Dietary management to maintain optimal Phe and Tyr levels proved to be challenging due to the presence of these two coexisting pathologies especially during infections and due to dietary non-compliance, necessitating frequent adjustments in the treatment strategy.

Conclusions: This case highlights the importance of considering multiple metabolic disorders in patients with unexplained clinical and biochemical findings. Early diagnosis and stringent dietary management are crucial for preventing neurological damage and ensuring favorable outcomes in patients with concurrent metabolic disorders.