Header

UZH-Logo

Maintenance Infos

6-Pyruvoyltetrahydropterin Synthase Deficiency: Review and Report of 28 Arab Subjects


Almannai, Mohammed; Felemban, Rana; Saleh, Mohammed A; Faqeih, Eissa A; Alasmari, Ali; AlHashem, Amal; Mohamed, Sarar; Sunbul, Rawda; Al-Murshedi, Fathiya; AlThihli, Khalid; Eyaid, Wafaa; Ali, Rehab; Ben-Omran, Tawfeg; Blau, Nenad; El-Hattab, Ayman W; Alfadhel, Majid (2019). 6-Pyruvoyltetrahydropterin Synthase Deficiency: Review and Report of 28 Arab Subjects. Pediatric Neurology, 96:40-47.

Abstract

BACKGROUND: Tetrahydrobiopterin is an essential cofactor for the hydroxylation of aromatic amino acids phenylalanine, tyrosine, and tryptophan. Therefore, tetrahydrobiopterin deficiency results in hyperphenylalaninemia as well as dopamine and serotonin depletion in the central nervous system. The enzyme 6-pyruvoyltetrahydropterin synthase catalyzes the second step of de novo synthesis of tetrahydrobiopterin, and its deficiency is the most frequent cause of tetrahydrobiopterin metabolism disorders. METHOD: We conducted a retrospective chart review of 28 subjects from 24 families with molecularly confirmed 6-pyruvoyltetrahydropterin synthase deficiency from six centers in three Arab countries. We reviewed clinical, biochemical, and molecular data. We also reviewed previously published cohorts of subjects with 6-pyruvoyltetrahydropterin synthase deficiency. RESULTS: Similar to previous observations, we show that early treatment (less than two months) is associated with better outcome. We identify eight PTS variants in 24 independent families. The most common variant is (c.238A>G; p.M80V) with an allele count of 33%. We also identify one novel variant (c.2T>G; p.?). CONCLUSION: The deficiency of 6-pyruvoyltetrahydropterin synthase is relatively common in the Arab population and should be considered in individuals with hyperphenylalaninemia. More natural history studies with comprehensive biochemical and molecular genetics data are needed for a robust base for the development of future therapy.

Abstract

BACKGROUND: Tetrahydrobiopterin is an essential cofactor for the hydroxylation of aromatic amino acids phenylalanine, tyrosine, and tryptophan. Therefore, tetrahydrobiopterin deficiency results in hyperphenylalaninemia as well as dopamine and serotonin depletion in the central nervous system. The enzyme 6-pyruvoyltetrahydropterin synthase catalyzes the second step of de novo synthesis of tetrahydrobiopterin, and its deficiency is the most frequent cause of tetrahydrobiopterin metabolism disorders. METHOD: We conducted a retrospective chart review of 28 subjects from 24 families with molecularly confirmed 6-pyruvoyltetrahydropterin synthase deficiency from six centers in three Arab countries. We reviewed clinical, biochemical, and molecular data. We also reviewed previously published cohorts of subjects with 6-pyruvoyltetrahydropterin synthase deficiency. RESULTS: Similar to previous observations, we show that early treatment (less than two months) is associated with better outcome. We identify eight PTS variants in 24 independent families. The most common variant is (c.238A>G; p.M80V) with an allele count of 33%. We also identify one novel variant (c.2T>G; p.?). CONCLUSION: The deficiency of 6-pyruvoyltetrahydropterin synthase is relatively common in the Arab population and should be considered in individuals with hyperphenylalaninemia. More natural history studies with comprehensive biochemical and molecular genetics data are needed for a robust base for the development of future therapy.

Statistics

Citations

Dimensions.ai Metrics
4 citations in Web of Science®
4 citations in Scopus®
Google Scholar™

Altmetrics

Downloads

26 downloads since deposited on 28 Jan 2020
20 downloads 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 > Pediatrics, Perinatology and Child Health
Life Sciences > Neurology
Life Sciences > Developmental Neuroscience
Health Sciences > Neurology (clinical)
Uncontrolled Keywords:Pediatrics, Perinatology, and Child Health, Developmental Neuroscience, Neurology, Clinical Neurology
Language:English
Date:1 July 2019
Deposited On:28 Jan 2020 12:03
Last Modified:29 Jul 2020 13:03
Publisher:Elsevier
ISSN:0887-8994
OA Status:Hybrid
Publisher DOI:https://doi.org/10.1016/j.pediatrneurol.2019.02.008
PubMed ID:30926181

Download

Hybrid Open Access

Download PDF  '6-Pyruvoyltetrahydropterin Synthase Deficiency: Review and Report of 28 Arab Subjects'.
Preview
Content: Published Version
Filetype: PDF
Size: 485kB
View at publisher
Licence: Creative Commons: Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)