Molecular genetics of phenylketonuria and tetrahydrobiopterin deficiency in Jordan
Carla Carducci,
Wajdi Amayreh,
Haneen Ababneh,
Amjad Mahasneh,
Buthaina Al Rababah,
Kefah Al Qaqa,
Momen Al Aqeel,
Cristiana Artiola,
Manuela Tolve,
Sirio D'Amici,
Nan Shen,
Yongguo Yu,
Alicia Hillert,
Nastassja Himmelreich,
Jürgen G. Okun,
Georg F. Hoffmann,
Nenad Blau
Affiliations
Carla Carducci
Department of Experimental Medicine University of Rome “La Sapienza” Rome Italy
Wajdi Amayreh
Queen Rania Children Hospital, King Hussein Medical Centre Amman Jordan
Haneen Ababneh
Princess Haya Biotechnology Centre Jordan University of Science and Technology Irbid Jordan
Amjad Mahasneh
Princess Haya Biotechnology Centre Jordan University of Science and Technology Irbid Jordan
Buthaina Al Rababah
Princess Haya Biotechnology Centre Jordan University of Science and Technology Irbid Jordan
Kefah Al Qaqa
Queen Rania Children Hospital, King Hussein Medical Centre Amman Jordan
Momen Al Aqeel
Queen Rania Children Hospital, King Hussein Medical Centre Amman Jordan
Cristiana Artiola
Department of Experimental Medicine University of Rome “La Sapienza” Rome Italy
Manuela Tolve
Department of Experimental Medicine University of Rome “La Sapienza” Rome Italy
Sirio D'Amici
Department of Experimental Medicine University of Rome “La Sapienza” Rome Italy
Nan Shen
Department of Rehabilitation Medicine Xin Hua Hospital affiliated to Shanghai Jiao Tong University School of Medicine Shanghai China
Yongguo Yu
Department of Pediatric Endocrinology and Genetic Metabolism Shanghai Institute for Pediatric Research, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University Shanghai China
Alicia Hillert
Dietmar Hopp Metabolic Center and Centre for Pediatrics and Adolescent Medicine University Hospital Heidelberg Heidelberg Germany
Nastassja Himmelreich
Dietmar Hopp Metabolic Center and Centre for Pediatrics and Adolescent Medicine University Hospital Heidelberg Heidelberg Germany
Jürgen G. Okun
Dietmar Hopp Metabolic Center and Centre for Pediatrics and Adolescent Medicine University Hospital Heidelberg Heidelberg Germany
Georg F. Hoffmann
Dietmar Hopp Metabolic Center and Centre for Pediatrics and Adolescent Medicine University Hospital Heidelberg Heidelberg Germany
Nenad Blau
Dietmar Hopp Metabolic Center and Centre for Pediatrics and Adolescent Medicine University Hospital Heidelberg Heidelberg Germany
Abstract 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 study documents 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.
