title: Proposed recommendations for diagnosing and managing individuals with glutaric aciduria type I: second revision.
abstract: Glutaric aciduria type I (GA-I; synonym, glutaric acidemia type I) is a rare inherited metabolic disease caused by deficiency of glutaryl-CoA dehydrogenase located in the catabolic pathways of L-lysine, L-hydroxylysine, and L-tryptophan. The enzymatic defect results in elevated concentrations of glutaric acid, 3-hydroxyglutaric acid, glutaconic acid, and glutaryl carnitine in body tissues, which can be reliably detected by gas chromatography/mass spectrometry (organic acids) and tandem mass spectrometry (acylcarnitines). Most untreated individuals with GA-I experience acute encephalopathic crises during the first 6 years of life that are triggered by infectious diseases, febrile reaction to vaccinations, and surgery. These crises result in striatal injury and consequent dystonic movement disorder; thus, significant mortality and morbidity results. In some patients, neurologic disease may also develop without clinically apparent crises at any age. Neonatal screening for GA-I us being used in a growing number of countries worldwide and is cost effective. Metabolic treatment, consisting of low lysine diet, carnitine supplementation, and intensified emergency treatment during catabolism, is effective treatment and improves neurologic outcome in those individuals diagnosed early; treatment after symptom onset, however, is less effective. Dietary treatment is relaxed after age 6 years and should be supervised by specialized metabolic centers. The major aim of this second revision of proposed recommendations is to re-evaluate the previous recommendations (Kölker et al. J Inherit Metab Dis 30:5-22, 2007b; J Inherit Metab Dis 34:677-694, 2011) and add new research findings, relevant clinical aspects, and the perspective of affected individuals.
authors.affiliation: Centre for Child and Adolescent Medicine, Department of General Paediatrics, Division of Neuropaediatrics and Metabolic Medicine, University Hospital Heidelberg, Im Neuenheimer Feld 430, D-69120, Heidelberg, Germany. Nikolas.Boy@med.uni-heidelberg.de.
authors.forename: Nikolas
authors.identifier: 0000-0001-7665-6602
authors.initials: N
authors.lastname: Boy
authors.affiliation: University Children's Hospital, University Medical Centre Hamburg-Eppendorf, Martinistrasse 52, D-20246, Hamburg, Germany.
authors.forename: Chris
authors.initials: C
authors.lastname: Mühlhausen
authors.affiliation: Dr. von Hauner Children's Hospital, Ludwig-Maximilians-University of Munich, University of Munich Medical Centre, Munich, Germany.
authors.forename: Esther M
authors.initials: EM
authors.lastname: Maier
authors.affiliation: Centre for Child and Adolescent Medicine, Department of General Paediatrics, Division of Neuropaediatrics and Metabolic Medicine, University Hospital Heidelberg, Im Neuenheimer Feld 430, D-69120, Heidelberg, Germany.
authors.forename: Jana
authors.initials: J
authors.lastname: Heringer
authors.affiliation: Centre for Child and Adolescent Medicine, Department of General Paediatrics, Division of Neuropaediatrics and Metabolic Medicine, University Hospital Heidelberg, Im Neuenheimer Feld 430, D-69120, Heidelberg, Germany.
authors.forename: Birgit
authors.initials: B
authors.lastname: Assmann
authors.affiliation: Centre for Child and Adolescent Medicine, Department of General Paediatrics, Division of Neuropaediatrics and Metabolic Medicine, University Hospital Heidelberg, Im Neuenheimer Feld 430, D-69120, Heidelberg, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Burgard
authors.affiliation: Dietetics, Great Ormond Street Hospital for Children, NHS Foundation Trust, London, UK.
authors.forename: Marjorie
authors.initials: M
authors.lastname: Dixon
authors.affiliation: Dr. von Hauner Children's Hospital, Ludwig-Maximilians-University of Munich, University of Munich Medical Centre, Munich, Germany.
authors.forename: Sandra
authors.initials: S
authors.lastname: Fleissner
authors.affiliation: Department of Pediatrics, Children's Hospital Health Sciences Centre and University of Manitoba, Winnipeg, MB, R3A 1R9, Canada.|Department of Biochemistry and Medical Genetics, Children's Hospital Health Sciences Centre and University of Manitoba, Winnipeg, MB, R3A 1R9, Canada.
authors.forename: Cheryl R
authors.initials: CR
authors.lastname: Greenberg
authors.affiliation: Centre for Child and Adolescent Medicine, Department of General Paediatrics, Division of Neuropaediatrics and Metabolic Medicine, University Hospital Heidelberg, Im Neuenheimer Feld 430, D-69120, Heidelberg, Germany.|Department of Neuroradiology, University Hospital Heidelberg, Heidelberg, Germany.
authors.forename: Inga
authors.initials: I
authors.lastname: Harting
authors.affiliation: Centre for Child and Adolescent Medicine, Department of General Paediatrics, Division of Neuropaediatrics and Metabolic Medicine, University Hospital Heidelberg, Im Neuenheimer Feld 430, D-69120, Heidelberg, Germany.
authors.forename: Georg F
authors.initials: GF
authors.lastname: Hoffmann
authors.affiliation: Clinic for Paediatrics I, Inherited Metabolic Disorders, Medical, University of Innsbruck, Innsbruck, Austria.
authors.forename: Daniela
authors.initials: D
authors.lastname: Karall
authors.affiliation: Department of Molecular & Medical Genetics, Oregon Health & Science University, Portland, OR, USA.
authors.forename: David M
authors.initials: DM
authors.lastname: Koeller
authors.affiliation: Justus Liebig University Giessen, Institute of Nutritional Science, Giessen, Germany.
authors.forename: Michael B
authors.initials: MB
authors.lastname: Krawinkel
authors.affiliation: Centre for Child and Adolescent Medicine, Department of General Paediatrics, Division of Neuropaediatrics and Metabolic Medicine, University Hospital Heidelberg, Im Neuenheimer Feld 430, D-69120, Heidelberg, Germany.
authors.forename: Jürgen G
authors.initials: JG
authors.lastname: Okun
authors.affiliation: Centre for Child and Adolescent Medicine, Department of General Paediatrics, Division of Neuropaediatrics and Metabolic Medicine, University Hospital Heidelberg, Im Neuenheimer Feld 430, D-69120, Heidelberg, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Opladen
authors.affiliation: Centre for Child and Adolescent Medicine, Department of General Paediatrics, Division of Neuropaediatrics and Metabolic Medicine, University Hospital Heidelberg, Im Neuenheimer Feld 430, D-69120, Heidelberg, Germany.
authors.forename: Roland
authors.initials: R
authors.lastname: Posset
authors.affiliation: Centre for Child and Adolescent Medicine, Department of General Paediatrics, Division of Neuropaediatrics and Metabolic Medicine, University Hospital Heidelberg, Im Neuenheimer Feld 430, D-69120, Heidelberg, Germany.
authors.forename: Katja
authors.initials: K
authors.lastname: Sahm
authors.affiliation: Division of Human Genetics, Medical University Innsbruck, Innsbruck, Austria.
authors.forename: Johannes
authors.initials: J
authors.lastname: Zschocke
authors.affiliation: Centre for Child and Adolescent Medicine, Department of General Paediatrics, Division of Neuropaediatrics and Metabolic Medicine, University Hospital Heidelberg, Im Neuenheimer Feld 430, D-69120, Heidelberg, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Kölker
mesh_terms: D000592:Amino Acid Metabolism, Inborn Errors / Q000175:diagnosis* / Q000188:drug therapy* / Q000378:metabolism; D001928:Brain Diseases, Metabolic / Q000175:diagnosis* / Q000188:drug therapy* / Q000378:metabolism; D019587:Dietary Supplements; D005977:Glutarates / Q000378:metabolism; D050770:Glutaryl-CoA Dehydrogenase / Q000172:deficiency* / Q000378:metabolism; D006801:Humans; D008239:Lysine / Q000378:metabolism
chemical_list: C108959:3-hydroxyglutaric acid; D005977:Glutarates; C010971:glutaconic acid; D050770:Glutaryl-CoA Dehydrogenase; C035736:glutaric acid; D008239:Lysine