title: Consensus guideline for the diagnosis and treatment of aromatic l-amino acid decarboxylase (AADC) deficiency.
abstract: Aromatic L-amino acid decarboxylase deficiency (AADCD) is a rare, autosomal recessive neurometabolic disorder that leads to a severe combined deficiency of serotonin, dopamine, norepinephrine and epinephrine. Onset is early in life, and key clinical symptoms are hypotonia, movement disorders (oculogyric crisis, dystonia, and hypokinesia), developmental delay, and autonomic symptoms.In this consensus guideline, representatives of the International Working Group on Neurotransmitter Related Disorders (iNTD) and patient representatives evaluated all available evidence for diagnosis and treatment of AADCD and made recommendations using SIGN and GRADE methodology. In the face of limited definitive evidence, we constructed practical recommendations on clinical diagnosis, laboratory diagnosis, imaging and electroencephalograpy, medical treatments and non-medical treatments. Furthermore, we identified topics for further research. We believe this guideline will improve the care for AADCD patients around the world whilst promoting general awareness of this rare disease.
authors.affiliation: Department of Neurology and Child Neurology, Radboud university medical center, Donders Institute for Brain, Cognition and Behaviour, Nijmegen, The Netherlands.
authors.forename: Tessa
authors.initials: T
authors.lastname: Wassenberg
authors.affiliation: Department of Clinical Biochemistry, CIBERER-ISCIII, Hospital Sant Joan de Déu Barcelona, Barcelona, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Molero-Luis
authors.affiliation: Department of Child Neurology and Metabolic Disorders, University Children's Hospital, Heidelberg, Germany.
authors.forename: Kathrin
authors.initials: K
authors.lastname: Jeltsch
authors.affiliation: Department of Child Neurology and Metabolic Disorders, University Children's Hospital, Heidelberg, Germany.
authors.forename: Georg F
authors.initials: GF
authors.lastname: Hoffmann
authors.affiliation: Department of Child Neurology and Metabolic Disorders, University Children's Hospital, Heidelberg, Germany.
authors.forename: Birgit
authors.initials: B
authors.lastname: Assmann
authors.affiliation: Dietmar-Hopp Metabolic Center, University Children's Hospital Heidelberg, Heidelberg, Germany.
authors.forename: Nenad
authors.initials: N
authors.lastname: Blau
authors.affiliation: Department of Child Neurology, CIBERER-ISCIII, Hospital Sant Joan de Déu Barcelona, Barcelona, Spain.
authors.forename: Angeles
authors.initials: A
authors.lastname: Garcia-Cazorla
authors.affiliation: Department of Clinical Biochemistry, CIBERER-ISCIII, Hospital Sant Joan de Déu Barcelona, Barcelona, Spain.
authors.forename: Rafael
authors.initials: R
authors.lastname: Artuch
authors.affiliation: First Department of Pediatrics, Pediatric Neurology Unit, Agia Sofia Hospital, National and Kapodistrian University of Athens, Athens, Greece.
authors.forename: Roser
authors.initials: R
authors.lastname: Pons
authors.affiliation: Department of Neurology, Washington University School of Medicine, St. Louis, USA.
authors.forename: Toni S
authors.initials: TS
authors.lastname: Pearson
authors.affiliation: Department of Pediatrics and Child Neuropsychiatry, Sapienza Università di Roma, Rome, Italy.
authors.forename: Vincenco
authors.initials: V
authors.lastname: Leuzzi
authors.affiliation: Department of Pediatrics and Child Neuropsychiatry, Sapienza Università di Roma, Rome, Italy.
authors.forename: Mario
authors.initials: M
authors.lastname: Mastrangelo
authors.affiliation: Department of Epilepsy and Clinical Neurophysiology, Boston Children's Hospital, Harvard Medical School, Boston, USA.
authors.forename: Phillip L
authors.initials: PL
authors.lastname: Pearl
authors.affiliation: Department of Pediatrics, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Wang Tso
authors.initials: WT
authors.lastname: Lee
authors.affiliation: Developmental Neurosciences, UCL- Institute of Child Health and Department of Neurology, Great Ormond Street Hospital for Children NHS Foundations Trust, London, UK.
authors.forename: Manju A
authors.initials: MA
authors.lastname: Kurian
authors.affiliation: Laboratory Medicine, Great Ormond Street Hospital and Neurometabolic Unit, National Hospital, London, UK.
authors.forename: Simon
authors.initials: S
authors.lastname: Heales
authors.affiliation: AADC research trust, London, UK.
authors.forename: Lisa
authors.initials: L
authors.lastname: Flint
authors.affiliation: Department of Neurology and Child Neurology, Radboud university medical center, Donders Institute for Brain, Cognition and Behaviour, Nijmegen, The Netherlands.|Department Laboratory Medicine, Alzheimer Centre, Radboud university medical center, Nijmegen, The Netherlands.
authors.forename: Marcel
authors.initials: M
authors.lastname: Verbeek
authors.affiliation: Department of Neurology and Child Neurology, Radboud university medical center, Donders Institute for Brain, Cognition and Behaviour, Nijmegen, The Netherlands.
authors.forename: Michèl
authors.initials: M
authors.lastname: Willemsen
authors.affiliation: Department of Child Neurology and Metabolic Disorders, University Children's Hospital, Heidelberg, Germany. Thomas.Opladen@med.uni-heidelberg.de.
authors.forename: Thomas
authors.initials: T
authors.lastname: Opladen
mesh_terms: D017668:Age of Onset; D000592:Amino Acid Metabolism, Inborn Errors / Q000097:blood / Q000134:cerebrospinal fluid / Q000175:diagnosis* / Q000628:therapy*; D001142:Aromatic-L-Amino-Acid Decarboxylases / Q000097:blood / Q000134:cerebrospinal fluid / Q000172:deficiency*; D018680:Cholinergic Antagonists / Q000627:therapeutic use; D018491:Dopamine Agonists / Q000627:therapeutic use; D017408:Guidelines as Topic; D006801:Humans; D008996:Monoamine Oxidase Inhibitors / Q000627:therapeutic use; D011388:Prolactin / Q000097:blood / Q000134:cerebrospinal fluid; D011732:Pyridoxal Phosphate / Q000627:therapeutic use
chemical_list: D018680:Cholinergic Antagonists; D018491:Dopamine Agonists; D008996:Monoamine Oxidase Inhibitors; D011732:Pyridoxal Phosphate; D011388:Prolactin; D001142:Aromatic-L-Amino-Acid Decarboxylases
keywords: AADC deficiency; Aromatic l-amino acid decarboxylase deficiency; Dopamine; GRADE; Guideline; Infantile dystonia-parkinsonism; Neurotransmitter; SIGN; Serotonin