Coexisting Genetic Disorders in Phenylketonuria: Clinical and Molecular Insights

Demirdöken E. D., Teke Kısa P., Kırmızıtaş M., Bilen M., Uzun Dinçtürk D., Kocabey M., ...Daha Fazla

17th Annual ICORD Meeting, İzmir, Türkiye, 14 - 16 Kasım 2025, ss.1-2, (Özet Bildiri)

  • Yayın Türü: Bildiri / Özet Bildiri
  • Basıldığı Şehir: İzmir
  • Basıldığı Ülke: Türkiye
  • Sayfa Sayıları: ss.1-2
  • Dokuz Eylül Üniversitesi Adresli: Evet

Özet

Coexisting Genetic Disorders in Phenylketonuria: Clinical and Molecular Insights

Emine Didem Demirdöken1,Pelin Teke Kısa1, Melis Kırmızıtaş1, Merve Bilen1, Duygu Uzun Dinçtürk1, Mehmet Kocabey2, Ahmet Okay Çağlayan2 , Özlem Giray Bozkaya3, Nur Arslan1

1Department of Pediatric Metabolism and Nutrition, Dokuz Eylul University Faculty of Medicine, Izmir, Turkey, 

2Department of Medical Genetics, Dokuz Eylul University Faculty of Medicine, Izmir, Turkey,

3Department of Pediatric Genetics, Dokuz Eylul University Faculty of Medicine, Izmir, Turkey,

 

 

Introduction

Phenylketonuria (PKU) is an autosomal recessive inherited metabolic disorder caused by pathogenic variants in the PAH gene, which encodes the phenylalanine hydroxylase (PAH) enzyme. In some cases, the clinical presentation cannot be fully explained by a single diagnosis. This study aimed to present the clinical and genetic characteristics of patients with phenylketonuria who were followed up in the metabolic outpatient clinic who were also diagnosed with an additional concomitant disease. 

 

Methods

The medical records of all patients diagnosed with phenylketonuria and followed up by the pediatric metabolic disorder department were retrospectively reviewed. Age, clinical history, findings, and genetic analysis results of patients with phenylketonuria with a coexisting diagnosis were recorded. 

Results

Among 473 patients diagnosed with phenylketonuria (PKU) and followed in our clinic, five were found to have an additional disease. All patients were referred to the metabolic outpatient clinic due to elevated phenylalanine levels detected in the national newborn screening program. In four of these patients, further biochemical and molecular genetic investigations were performed during follow-up because of the clinical and biochemical findings that could not be explanied by PKU alone, leading to the diagnosis of a second disorder. One patient was diagnosed with Duchenne muscular dystrıphy due to persistent elevations of creatine kinase levels; another with congenital hemolytic anemia based on anemia and reticulocytosis; one with dihydropteridine reductase deficiency due to early-onset seizures and ataxia; and another with glucose-6-phosphate dehydrogenase deficiency identified through whole-exome sequencing performed for developmental delay.

Conclusion

Although coexisting diagnoses are rare among metabolic and genetic disorders, they substantially complicate the clinical course and patient management. The possibility of a second genetic disorder should be considered in patients presenting with atypical features or a clinical course that deviates from expectations. In the follow-up of individuals with phenylketonuria, it is essential not to rely solely on phenylalanine levels but to evaluate advanced biochemical and genetic analyses according to the evolution of clinical findings. Therefore, recognizing the possibility of dual diagnoses in patients with phenylketonuria with atypical clinical manifestations is crucial for accurate diagnosis and effective management.