Carducci Carla, Amayreh Wajdi, Ababneh Haneen, Mahasneh Amjad, Al Rababah Buthaina, Al Qaqa Kefah, Al Aqeel Momen, Artiola Cristiana, Tolve Manuela, D'Amici Sirio, Shen Nan, Yu Yongguo, Hillert Alicia, Himmelreich Nastassja, Okun Jürgen G, Hoffmann Georg F, Blau Nenad
Department of Experimental Medicine University of Rome "La Sapienza" Rome Italy.
Queen Rania Children Hospital, King Hussein Medical Centre Amman Jordan.
JIMD Rep. 2020 May 19;55(1):59-67. doi: 10.1002/jmd2.12130. eCollection 2020 Sep.
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.
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.
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 (BH) metabolism.
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 BH deficiencies within HPA patients. With one exception, all patients were homozygous for particular gene variants.
This approach enables differentiation between PKU and BH deficiencies and, thus, allows for critical selection of a specific treatment strategies.
与世界其他地区相比，中东地区苯丙酮尿症（PKU）患病率的相关信息匮乏，这可能是由于国家新生儿筛查项目实施困难所致。
本研究首次对约旦安曼侯赛因国王医疗中心儿科代谢遗传学诊所诊断为高苯丙氨酸血症（HPA）的患者进行基因分型并进行生化特征分析。
共对33例HPA患者和55名家庭成员的干血斑进行了蝶呤（新蝶呤和生物蝶呤）和二氢蝶啶还原酶（DHPR）活性检测。对HPA患者进行苯丙酮尿症（PKU）及四氢生物蝶呤（BH4）代谢相关基因的基因分型。
共有20例患者因苯丙氨酸羟化酶（PAH）缺乏被诊断为PKU，2例因鸟苷三磷酸环化水合酶I（GTPCH）缺乏，6例因DHPR缺乏，3例因6-丙酮酰四氢蝶呤合酶（PTPS）缺乏。2例患者无法确诊。本研究记录了HPA患者中BH4缺乏的高比例情况。除1例例外，所有患者均为特定基因变异的纯合子。
这种方法能够区分PKU和BH4缺乏，从而有助于关键地选择特定的治疗策略。
