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Incidence, disease onset and short-term outcome in urea cycle disorders –cross-border surveillance in Germany, Austria and Switzerland

BACKGROUND: Urea cycle disorders (UCDs) are a group of rare inherited metabolic disorders. Affected individuals often present with hyperammonemic encephalopathy (HE) and have an increased risk of severe neurologic disease and early death. The study aims to provide epidemiologic data and to describe...

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Autores principales: Nettesheim, Susanne, Kölker, Stefan, Karall, Daniela, Häberle, Johannes, Posset, Roland, Hoffmann, Georg F., Heinrich, Beate, Gleich, Florian, Garbade, Sven F.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5472961/
https://www.ncbi.nlm.nih.gov/pubmed/28619060
http://dx.doi.org/10.1186/s13023-017-0661-x
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author Nettesheim, Susanne
Kölker, Stefan
Karall, Daniela
Häberle, Johannes
Posset, Roland
Hoffmann, Georg F.
Heinrich, Beate
Gleich, Florian
Garbade, Sven F.
author_facet Nettesheim, Susanne
Kölker, Stefan
Karall, Daniela
Häberle, Johannes
Posset, Roland
Hoffmann, Georg F.
Heinrich, Beate
Gleich, Florian
Garbade, Sven F.
author_sort Nettesheim, Susanne
collection PubMed
description BACKGROUND: Urea cycle disorders (UCDs) are a group of rare inherited metabolic disorders. Affected individuals often present with hyperammonemic encephalopathy (HE) and have an increased risk of severe neurologic disease and early death. The study aims to provide epidemiologic data and to describe the disease manifestation and short-term outcome. METHOD: Cross-border surveillance of newly diagnosed patients with UCDs - below 16 years of age - was performed from July 2012 to June 2015 in Germany and Austria and from January 2012 to December 2015 in Switzerland. Inquiries were sent monthly to all Pediatric Departments in Germany and Switzerland, and quarterly to the Austrian Metabolic Group. In addition, data were collected via a second source (metabolic laboratories) in all three countries. RESULTS: Between July 2012 and June 2015, fifty patients (Germany: 39, Austria: 7, Switzerland: 4) with newly diagnosed UCDs were reported and later confirmed resulting in an estimated cumulative incidence of 1 in 51,946 live births. At diagnosis, thirty-nine patients were symptomatic and 11 asymptomatic [10 identified by newborn screening (NBS), 1 by high-risk-family screening (HRF)]. The majority of symptomatic patients (30 of 39 patients) developed HE with (n = 25) or without coma (n = 5), 28 of them with neonatal onset. Despite emergency treatment 15 of 30 patients with HE already died during the newborn period. Noteworthy, 10 of 11 patients diagnosed by NBS or HRF remained asymptomatic. Comparison with the European registry and network for intoxication type metabolic diseases (E-IMD) demonstrated that cross-national surveillance identified a higher number of clinically severe UCD patients characterized by earlier onset of symptoms, higher peak ammonium concentrations in plasma and higher mortality. CONCLUSION: Cross-border surveillance is a powerful tool to identify patients with UCDs demonstrating that (1) the cumulative incidence of UCDs is lower than originally suggested, (2) the mortality rate is still high in patients with neonatal onset of symptoms, and (3) onset type and peak plasma ammonium concentration predict mortality.
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spelling pubmed-54729612017-06-21 Incidence, disease onset and short-term outcome in urea cycle disorders –cross-border surveillance in Germany, Austria and Switzerland Nettesheim, Susanne Kölker, Stefan Karall, Daniela Häberle, Johannes Posset, Roland Hoffmann, Georg F. Heinrich, Beate Gleich, Florian Garbade, Sven F. Orphanet J Rare Dis Research BACKGROUND: Urea cycle disorders (UCDs) are a group of rare inherited metabolic disorders. Affected individuals often present with hyperammonemic encephalopathy (HE) and have an increased risk of severe neurologic disease and early death. The study aims to provide epidemiologic data and to describe the disease manifestation and short-term outcome. METHOD: Cross-border surveillance of newly diagnosed patients with UCDs - below 16 years of age - was performed from July 2012 to June 2015 in Germany and Austria and from January 2012 to December 2015 in Switzerland. Inquiries were sent monthly to all Pediatric Departments in Germany and Switzerland, and quarterly to the Austrian Metabolic Group. In addition, data were collected via a second source (metabolic laboratories) in all three countries. RESULTS: Between July 2012 and June 2015, fifty patients (Germany: 39, Austria: 7, Switzerland: 4) with newly diagnosed UCDs were reported and later confirmed resulting in an estimated cumulative incidence of 1 in 51,946 live births. At diagnosis, thirty-nine patients were symptomatic and 11 asymptomatic [10 identified by newborn screening (NBS), 1 by high-risk-family screening (HRF)]. The majority of symptomatic patients (30 of 39 patients) developed HE with (n = 25) or without coma (n = 5), 28 of them with neonatal onset. Despite emergency treatment 15 of 30 patients with HE already died during the newborn period. Noteworthy, 10 of 11 patients diagnosed by NBS or HRF remained asymptomatic. Comparison with the European registry and network for intoxication type metabolic diseases (E-IMD) demonstrated that cross-national surveillance identified a higher number of clinically severe UCD patients characterized by earlier onset of symptoms, higher peak ammonium concentrations in plasma and higher mortality. CONCLUSION: Cross-border surveillance is a powerful tool to identify patients with UCDs demonstrating that (1) the cumulative incidence of UCDs is lower than originally suggested, (2) the mortality rate is still high in patients with neonatal onset of symptoms, and (3) onset type and peak plasma ammonium concentration predict mortality. BioMed Central 2017-06-15 /pmc/articles/PMC5472961/ /pubmed/28619060 http://dx.doi.org/10.1186/s13023-017-0661-x Text en © The Author(s). 2017 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Nettesheim, Susanne
Kölker, Stefan
Karall, Daniela
Häberle, Johannes
Posset, Roland
Hoffmann, Georg F.
Heinrich, Beate
Gleich, Florian
Garbade, Sven F.
Incidence, disease onset and short-term outcome in urea cycle disorders –cross-border surveillance in Germany, Austria and Switzerland
title Incidence, disease onset and short-term outcome in urea cycle disorders –cross-border surveillance in Germany, Austria and Switzerland
title_full Incidence, disease onset and short-term outcome in urea cycle disorders –cross-border surveillance in Germany, Austria and Switzerland
title_fullStr Incidence, disease onset and short-term outcome in urea cycle disorders –cross-border surveillance in Germany, Austria and Switzerland
title_full_unstemmed Incidence, disease onset and short-term outcome in urea cycle disorders –cross-border surveillance in Germany, Austria and Switzerland
title_short Incidence, disease onset and short-term outcome in urea cycle disorders –cross-border surveillance in Germany, Austria and Switzerland
title_sort incidence, disease onset and short-term outcome in urea cycle disorders –cross-border surveillance in germany, austria and switzerland
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5472961/
https://www.ncbi.nlm.nih.gov/pubmed/28619060
http://dx.doi.org/10.1186/s13023-017-0661-x
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