title: Tetrahydrobiopterin deficiency among Serbian patients presenting with hyperphenylalaninemia.
abstract: Hyperphenylalaninemia (HPA) [phenylketonuria (PKU) and tetrahydrobiopterin (BH4) deficiencies] is rare inborn metabolic disease characterized by elevated phenylalanine level in body fluids. In Serbia, 62 HPA patients have been identified through newborn screening since 1983. However, pterin pattern analysis is not performed. We present a patient initially diagnosed and treated as classical PKU. At 3 years of age, during infection with H1N1 influenza A virus, the patient first developed a neurologic crisis with encephalopathy and dystonic movements. We suspected that the patient is the first case of BH4 deficiency identified in Serbia. Genetic analyses showed that the patient does not have disease-causing variants of the PAH gene and carries a p.Asp136Val mutation in homozygous state in the PTS gene. For patients with treatable rare diseases, like PKU and BH4 deficiencies, correct diagnosis is crucial for the implementation of optimal treatment. If biochemical tests needed for differential diagnosis are not available, our experience emphasizes the necessity of immediate genetic testing after newborn screening.
authors.forename: Maja
authors.initials: M
authors.lastname: Stojiljkovic
authors.forename: Kristel
authors.initials: K
authors.lastname: Klaassen
authors.forename: Maja
authors.initials: M
authors.lastname: Djordjevic
authors.forename: Adrijan
authors.initials: A
authors.lastname: Sarajlija
authors.forename: Bozica
authors.initials: B
authors.lastname: Kecman
authors.forename: Milena
authors.initials: M
authors.lastname: Ugrin
authors.forename: Branka
authors.initials: B
authors.lastname: Zukic
authors.forename: Lourdes R
authors.initials: LR
authors.lastname: Desviat
authors.forename: Sonja
authors.initials: S
authors.lastname: Pavlovic
authors.forename: Belen
authors.initials: B
authors.lastname: Perez
mesh_terms: D001708:Biopterins / Q000172:deficiency; D006801:Humans; D007231:Infant, Newborn; D053118:Influenza A Virus, H1N1 Subtype; D007251:Influenza, Human / Q000150:complications; D008297:Male; D010651:Phenylalanine Hydroxylase / Q000235:genetics; D010661:Phenylketonurias / Q000150:complications / Q000235:genetics / Q000473:pathology*; D055771:Serbia
chemical_list: D001708:Biopterins; D010651:Phenylalanine Hydroxylase