Molecular genetics of phenylketonuria and tetrahydrobiopterin deficiency in Jordan.

Carla Carducci,Momen Al Aqeel,Kefah Al Qaqa,Sirio D'Amici,Wajdi Amayreh,Jürgen G Okun,Buthaina Al Rababah,Georg F Hoffmann,Nan Shen,Cristiana Artiola,Manuela Tolve,Alicia Hillert,Amjad Mahasneh,Nastassja Himmelreich,Haneen Ababneh,Nenad Blau,Yongguo Yu

doi:10.1002/jmd2.12130

Abstract

BackgroundInformation 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.ObjectiveThis 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.MethodsA 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.ResultsIn 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.ConclusionsThis approach enables differentiation between PKU and BH4 deficiencies and, thus, allows for critical selection of a specific treatment strategies.

Highlights

Phenylketonuria (PKU; OMIM# 261600) is an autosomal recessive metabolic disease caused by deficiency of hepatic phenylalanine-4-hydroxylase (PAH; EC 1.14.16.1).[1]
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
In total 20 patients were diagnosed with PKU due to phenylalanine hydroxylase (PAH) deficiency, 2 with GTP cyclohydrolase I (GTPCH) deficiency, 6 with dihydropteridine reductase (DHPR) deficiency, and 3 with the 6-pyruvoyl-tetrahydropterin synthase (PTPS) deficiency

Summary

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. This study documents a high percentage of BH4 deficiencies within HPA patients. All patients were homozygous for particular gene variants

Conclusions

| INTRODUCTION

| MATERIALS AND METHODS

Findings

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| DISCUSSION