Journal article
Age at disease onset and peak ammonium level rather than interventional variables predict the neurological outcome in urea cycle disorders.
- Posset R Department of General Pediatrics, Division of Inherited Metabolic Diseases, University Children's Hospital Heidelberg, Im Neuenheimer Feld 430, D-69120, Heidelberg, Germany. roland.posset@med.uni-heidelberg.de.
- Garcia-Cazorla A Hospital San Joan de Deu, Servicio de Neurologia and CIBERER, ISCIII, Barcelona, Spain.
- Valayannopoulos V Assistance Publique-Hôpitaux de Paris, Service de Maladies Metaboliques, Hôpital Necker-Enfants Malades, Paris, France.
- Teles EL Hospital de S. João, EPE, Unidade de Doenças Metabólicas, Serviço de Pediatria, Porto, Portugal.
- Dionisi-Vici C Ospedale Pediatrico Bambino Gésu, U.O.C. Patologia Metabolica, Rome, Italy.
- Brassier A Assistance Publique-Hôpitaux de Paris, Service de Maladies Metaboliques, Hôpital Necker-Enfants Malades, Paris, France.
- Burlina AB Azienda Ospedaliera di Padova, U.O.C. Malattie Metaboliche Ereditarie, Padova, Italy.
- Burgard P Department of General Pediatrics, Division of Inherited Metabolic Diseases, University Children's Hospital Heidelberg, Im Neuenheimer Feld 430, D-69120, Heidelberg, Germany.
- Cortès-Saladelafont E Hospital San Joan de Deu, Servicio de Neurologia and CIBERER, ISCIII, Barcelona, Spain.
- Dobbelaere D Centre de Référence Maladies Héréditaires du Métabolisme de l'Enfant et de l'Adulte, Jeanne de Flandre Hospital, CHRU Lille, and RADEME EA 7364, Faculty of Medicine, University Lille 2, Lille, 59037, France.
- Couce ML Metabolic Unit, Department of Pediatrics, Hospital Clinico Universitario de Santiago de Compostela, Santiago de Compostela, Spain.
- Sykut-Cegielska J Screening Department, Institute of Mother and Child, Warsaw, Poland.
- Häberle J Division of Metabolism and Children's Research Centre, University Children's Hospital Zurich, Steinwiesstraße 75, CH-8032, Zurich, Switzerland.
- Lund AM Centre for Inherited Metabolic Diseases, Department of Clinical Genetics, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
- Chakrapani A Birmingham Children's Hospital NHS Foundation Trust, Steelhouse Lane, Birmingham, B4 6NH, UK.
- Schiff M Hôpital Robert Debré, Reference Centre for Inborn Errors of Metabolism, APHP and Université Paris-Diderot, Paris, France.
- Walter JH Manchester Academic Health Science Centre, Willink Biochemical Genetics Unit, Genetic Medicine, University of Manchester, Manchester, UK.
- Zeman J First Faculty of Medicine, Charles University and General University of Prague, Prague, Czech Republic.
- Vara R Evelina Children's Hospital, St Thomas' Hospital, London, UK.
- Kölker S Department of General Pediatrics, Division of Inherited Metabolic Diseases, University Children's Hospital Heidelberg, Im Neuenheimer Feld 430, D-69120, Heidelberg, Germany.
- 2016-04-24
Published in:
- Journal of inherited metabolic disease. - 2016
Adolescent
Amino Acid Metabolism, Inborn Errors
Ammonium Compounds
Argininosuccinate Synthase
Child
Citrullinemia
Female
Humans
Hyperammonemia
Infant, Newborn
Late Onset Disorders
Male
Neonatal Screening
Nervous System Diseases
Prospective Studies
Urea
Urea Cycle Disorders, Inborn
English
BACKGROUND
Patients with urea cycle disorders (UCDs) have an increased risk of neurological disease manifestation.
AIMS
Determining the effect of diagnostic and therapeutic interventions on the neurological outcome.
METHODS
Evaluation of baseline, regular follow-up and emergency visits of 456 UCD patients prospectively followed between 2011 and 2015 by the E-IMD patient registry.
RESULTS
About two-thirds of UCD patients remained asymptomatic until age 12 days [i.e. the median age at diagnosis of patients identified by newborn screening (NBS)] suggesting a potential benefit of NBS. In fact, NBS lowered the age at diagnosis in patients with late onset of symptoms (>28 days), and a trend towards improved long-term neurological outcome was found for patients with argininosuccinate synthetase and lyase deficiency as well as argininemia identified by NBS. Three to 17 different drug combinations were used for maintenance therapy, but superiority of any single drug or specific drug combination above other combinations was not demonstrated. Importantly, non-interventional variables of disease severity, such as age at disease onset and peak ammonium level of the initial hyperammonemic crisis (cut-off level: 500 μmol/L) best predicted the neurological outcome.
CONCLUSIONS
Promising results of NBS for late onset UCD patients are reported and should be re-evaluated in a larger and more advanced age group. However, non-interventional variables affect the neurological outcome of UCD patients. Available evidence-based guideline recommendations are currently heterogeneously implemented into practice, leading to a high variability of drug combinations that hamper our understanding of optimised long-term and emergency treatment.
Patients with urea cycle disorders (UCDs) have an increased risk of neurological disease manifestation.
AIMS
Determining the effect of diagnostic and therapeutic interventions on the neurological outcome.
METHODS
Evaluation of baseline, regular follow-up and emergency visits of 456 UCD patients prospectively followed between 2011 and 2015 by the E-IMD patient registry.
RESULTS
About two-thirds of UCD patients remained asymptomatic until age 12 days [i.e. the median age at diagnosis of patients identified by newborn screening (NBS)] suggesting a potential benefit of NBS. In fact, NBS lowered the age at diagnosis in patients with late onset of symptoms (>28 days), and a trend towards improved long-term neurological outcome was found for patients with argininosuccinate synthetase and lyase deficiency as well as argininemia identified by NBS. Three to 17 different drug combinations were used for maintenance therapy, but superiority of any single drug or specific drug combination above other combinations was not demonstrated. Importantly, non-interventional variables of disease severity, such as age at disease onset and peak ammonium level of the initial hyperammonemic crisis (cut-off level: 500 μmol/L) best predicted the neurological outcome.
CONCLUSIONS
Promising results of NBS for late onset UCD patients are reported and should be re-evaluated in a larger and more advanced age group. However, non-interventional variables affect the neurological outcome of UCD patients. Available evidence-based guideline recommendations are currently heterogeneously implemented into practice, leading to a high variability of drug combinations that hamper our understanding of optimised long-term and emergency treatment.
- Language
-
- English
- Open access status
- closed
- Identifiers
-
- DOI 10.1007/s10545-016-9938-9
- PMID 27106216
- Persistent URL
- https://folia.unifr.ch/global/documents/255482
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