Ricerc@Sapienza

Background: Information regarding the prevalence of PKU in the Middle East
in comparison to other world regions is scarce, which might be explained by
difficulties in the implementation of national newborn screening programs.
Objective: This study seeks for the first time to genotype and biochemically
characterize patients diagnosed with hyperphenylalaninemia (HPA) at the
Pediatric Metabolic Genetics Clinic at the King Hussein Medical Center,
Amman, Jordan.
Methods: A total of 33 patients with HPA and 55 family members were investigated
for pterins (neopterin and biopterin) and dihydropteridine reductase
(DHPR) activity in dried blood spots. Patients with HPA were genotyped for
phenylketonuria (PKU) and the genes involved in tetrahydrobiopterin (BH4)
metabolism.
Results: In total 20 patients were diagnosed with PKU due to phenylalanine
hydroxylase (PAH) deficiency, 2 with GTP cyclohydrolase I (GTPCH) deficiency,
6 with DHPR deficiency, and 3 with the 6-pyruvoyl-tetrahydropterin
synthase (PTPS) deficiency. Diagnosis was not possible in 2 patients.
This studydocuments a high percentage of BH4 deficiencies within HPA patients. With
one exception, all patients were homozygous for particular gene variants.
Conclusions: This approach enables differentiation between PKU and BH4
deficiencies and, thus, allows for critical selection of a specific treatment
strategies.