Tetrahydrobiopterin deficiency among Serbian patients presenting with hyperphenylalaninemia
-
Maja Stojiljkovic
,
Kristel Klaassen
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.
Acknowledgments
This work has been funded by the Ministry of Education, Science and Technological Development, Republic of Serbia (grant no. III 41004); the Spanish-Serbian cooperation project funded by the Ministry of Economy and Competitiveness, Spain (PRI-AIBSE-2011-1126); and the Ministry of Education, Science, and Technological Development, Republic of Serbia (451-03-02635/2011-14/14).
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©2015 by De Gruyter
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