Orphanet Journal of Rare Diseases (May 2020)
Consensus guideline for the diagnosis and treatment of tetrahydrobiopterin (BH4) deficiencies
- Thomas Opladen,
- Eduardo López-Laso,
- Elisenda Cortès-Saladelafont,
- Toni S. Pearson,
- H. Serap Sivri,
- Yilmaz Yildiz,
- Birgit Assmann,
- Manju A. Kurian,
- Vincenzo Leuzzi,
- Simon Heales,
- Simon Pope,
- Francesco Porta,
- Angeles García-Cazorla,
- Tomáš Honzík,
- Roser Pons,
- Luc Regal,
- Helly Goez,
- Rafael Artuch,
- Georg F. Hoffmann,
- Gabriella Horvath,
- Beat Thöny,
- Sabine Scholl-Bürgi,
- Alberto Burlina,
- Marcel M. Verbeek,
- Mario Mastrangelo,
- Jennifer Friedman,
- Tessa Wassenberg,
- Kathrin Jeltsch,
- Jan Kulhánek,
- Oya Kuseyri Hübschmann,
- on behalf of the International Working Group on Neurotransmitter related Disorders (iNTD)
Affiliations
- Thomas Opladen
- Division of Child Neurology and Metabolic Disorders, University Children’s Hospital
- Eduardo López-Laso
- Pediatric Neurology Unit, Department of Pediatrics, University Hospital Reina Sofía, IMIBIC and CIBERER
- Elisenda Cortès-Saladelafont
- Inborn errors of metabolism Unit, Institut de Recerca Sant Joan de Déu and CIBERER-ISCIII
- Toni S. Pearson
- Department of Neurology, Washington University School of Medicine
- H. Serap Sivri
- Department of Pediatrics, Section of Metabolism, Hacettepe University, Faculty of Medicine
- Yilmaz Yildiz
- Department of Pediatrics, Section of Metabolism, Hacettepe University, Faculty of Medicine
- Birgit Assmann
- Division of Child Neurology and Metabolic Disorders, University Children’s Hospital
- Manju A. Kurian
- Developmental Neurosciences, UCL Great Ormond Street-Institute of Child Health
- Vincenzo Leuzzi
- Unit of Child Neurology and Psychiatry, Department of Human Neuroscience, Sapienza University of Rome
- Simon Heales
- Neurometabolic Unit, National Hospital
- Simon Pope
- Neurometabolic Unit, National Hospital
- Francesco Porta
- Department of Pediatrics, AOU Città della Salute e della Scienza
- Angeles García-Cazorla
- Inborn errors of metabolism Unit, Institut de Recerca Sant Joan de Déu and CIBERER-ISCIII
- Tomáš Honzík
- Department of Paediatrics and Adolescent Medicine, First Faculty of Medicine, Charles University and General University Hospital in Prague
- Roser Pons
- First Department of Pediatrics of the University of Athens, Aghia Sofia Hospital
- Luc Regal
- Department of Pediatric, Pediatric Neurology and Metabolism Unit, UZ Brussel
- Helly Goez
- Department of Pediatrics, University of Alberta Glenrose Rehabilitation Hospital
- Rafael Artuch
- Clinical biochemistry department, Institut de Recerca Sant Joan de Déu, CIBERER and MetabERN Hospital Sant Joan de Déu
- Georg F. Hoffmann
- Division of Child Neurology and Metabolic Disorders, University Children’s Hospital
- Gabriella Horvath
- Department of Pediatrics, Division of Biochemical Genetics, BC Children’s Hospital, University of British Columbia
- Beat Thöny
- Division of Metabolism, University Children’s Hospital Zurich
- Sabine Scholl-Bürgi
- Clinic for Pediatrics I, Medical University of Innsbruck
- Alberto Burlina
- U.O.C. Malattie Metaboliche Ereditarie, Dipartimento della Salute della Donna e del Bambino, Azienda Ospedaliera Universitaria di Padova - Campus Biomedico Pietro d’Abano
- Marcel M. Verbeek
- Departments of Neurology and Laboratory Medicine, Alzheimer Centre, Radboud University Medical Center, Donders Institute for Brain, Cognition and Behaviour
- Mario Mastrangelo
- Unit of Child Neurology and Psychiatry, Department of Human Neuroscience, Sapienza University of Rome
- Jennifer Friedman
- UCSD Departments of Neuroscience and Pediatrics, Rady Children’s Hospital Division of Neurology; Rady Children’s Institute for Genomic Medicine
- Tessa Wassenberg
- Department of Pediatric, Pediatric Neurology and Metabolism Unit, UZ Brussel
- Kathrin Jeltsch
- Division of Child Neurology and Metabolic Disorders, University Children’s Hospital
- Jan Kulhánek
- Department of Paediatrics and Adolescent Medicine, First Faculty of Medicine, Charles University and General University Hospital in Prague
- Oya Kuseyri Hübschmann
- Division of Child Neurology and Metabolic Disorders, University Children’s Hospital
- on behalf of the International Working Group on Neurotransmitter related Disorders (iNTD)
- DOI
- https://doi.org/10.1186/s13023-020-01379-8
- Journal volume & issue
-
Vol. 15,
no. 1
pp. 1 – 30
Abstract
Abstract Background Tetrahydrobiopterin (BH4) deficiencies comprise a group of six rare neurometabolic disorders characterized by insufficient synthesis of the monoamine neurotransmitters dopamine and serotonin due to a disturbance of BH4 biosynthesis or recycling. Hyperphenylalaninemia (HPA) is the first diagnostic hallmark for most BH4 deficiencies, apart from autosomal dominant guanosine triphosphate cyclohydrolase I deficiency and sepiapterin reductase deficiency. Early supplementation of neurotransmitter precursors and where appropriate, treatment of HPA results in significant improvement of motor and cognitive function. Management approaches differ across the world and therefore these guidelines have been developed aiming to harmonize and optimize patient care. Representatives of the International Working Group on Neurotransmitter related Disorders (iNTD) developed the guidelines according to the SIGN (Scottish Intercollegiate Guidelines Network) methodology by evaluating all available evidence for the diagnosis and treatment of BH4 deficiencies. Conclusion Although the total body of evidence in the literature was mainly rated as low or very low, these consensus guidelines will help to harmonize clinical practice and to standardize and improve care for BH4 deficient patients.
Keywords
- Tetrahydrobiopterin deficiency
- BH4
- Neurotransmitter
- Guanosine triphosphate cyclohydrolase deficiency
- 6-pyruvoyltetrahydropterin synthase deficiency
- Sepiapterin reductase deficiency, pterin-4-alpha-carbinolamine dehydratase deficiency
