Header

UZH-Logo

Maintenance Infos

Molecular genetics of phenylketonuria and tetrahydrobiopterin deficiency in Jordan


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 (BH$_{4}$) 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 BH$_{4}$ deficiencies within HPA patients. With one exception, all patients were homozygous for particular gene variants.

Conclusions

This approach enables differentiation between PKU and BH$_{4}$ deficiencies and, thus, allows for critical selection of a specific treatment strategies.

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 (BH$_{4}$) 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 BH$_{4}$ deficiencies within HPA patients. With one exception, all patients were homozygous for particular gene variants.

Conclusions

This approach enables differentiation between PKU and BH$_{4}$ deficiencies and, thus, allows for critical selection of a specific treatment strategies.

Statistics

Citations

Dimensions.ai Metrics

Altmetrics

Downloads

1 download since deposited on 18 Jan 2021
1 download since 12 months
Detailed statistics

Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Children's Hospital Zurich > Medical Clinic
Dewey Decimal Classification:610 Medicine & health
Scopus Subject Areas:Health Sciences > Internal Medicine
Health Sciences > Endocrinology, Diabetes and Metabolism
Life Sciences > Biochemistry, Genetics and Molecular Biology (miscellaneous)
Language:German
Date:September 2020
Deposited On:18 Jan 2021 15:43
Last Modified:01 Feb 2021 16:24
Publisher:Springer
ISSN:2192-8304
OA Status:Gold
Free access at:PubMed ID. An embargo period may apply.
Publisher DOI:https://doi.org/10.1002/jmd2.12130
PubMed ID:32905092

Download

Gold Open Access

Download PDF  'Molecular genetics of phenylketonuria and tetrahydrobiopterin deficiency in Jordan'.
Preview
Content: Published Version
Filetype: PDF
Size: 1MB
View at publisher
Licence: Creative Commons: Attribution 4.0 International (CC BY 4.0)