Incidence, disease onset and short-term outcome in urea cycle disorders –cross-border surveillance in Germany, Austria and Switzerland
Abstract 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 d...
Main Authors: | , , , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
BMC
2017-06-01
|
Series: | Orphanet Journal of Rare Diseases |
Subjects: | |
Online Access: | http://link.springer.com/article/10.1186/s13023-017-0661-x |
id |
doaj-23370ecb154343929b185a6fd1033613 |
---|---|
record_format |
Article |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Susanne Nettesheim Stefan Kölker Daniela Karall Johannes Häberle Roland Posset Georg F. Hoffmann Beate Heinrich Florian Gleich Sven F. Garbade On behalf of Arbeitsgemeinschaft für Pädiatrische Stoffwechselstörungen (APS); European registry and network for Intoxication type Metabolic Diseases (E-IMD); Erhebungseinheit für Seltene Pädiatrische Erkrankungen in Deutschland (ESPED); Austrian Metabolic Group; Swiss Paediatric Surveillance Unit (SPSU) |
spellingShingle |
Susanne Nettesheim Stefan Kölker Daniela Karall Johannes Häberle Roland Posset Georg F. Hoffmann Beate Heinrich Florian Gleich Sven F. Garbade On behalf of Arbeitsgemeinschaft für Pädiatrische Stoffwechselstörungen (APS); European registry and network for Intoxication type Metabolic Diseases (E-IMD); Erhebungseinheit für Seltene Pädiatrische Erkrankungen in Deutschland (ESPED); Austrian Metabolic Group; Swiss Paediatric Surveillance Unit (SPSU) Incidence, disease onset and short-term outcome in urea cycle disorders –cross-border surveillance in Germany, Austria and Switzerland Orphanet Journal of Rare Diseases Urea cycle disorder(s) Hyperammonemia Incidence Mortality Newborn screening Outcome |
author_facet |
Susanne Nettesheim Stefan Kölker Daniela Karall Johannes Häberle Roland Posset Georg F. Hoffmann Beate Heinrich Florian Gleich Sven F. Garbade On behalf of Arbeitsgemeinschaft für Pädiatrische Stoffwechselstörungen (APS); European registry and network for Intoxication type Metabolic Diseases (E-IMD); Erhebungseinheit für Seltene Pädiatrische Erkrankungen in Deutschland (ESPED); Austrian Metabolic Group; Swiss Paediatric Surveillance Unit (SPSU) |
author_sort |
Susanne Nettesheim |
title |
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_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_sort |
incidence, disease onset and short-term outcome in urea cycle disorders –cross-border surveillance in germany, austria and switzerland |
publisher |
BMC |
series |
Orphanet Journal of Rare Diseases |
issn |
1750-1172 |
publishDate |
2017-06-01 |
description |
Abstract 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. |
topic |
Urea cycle disorder(s) Hyperammonemia Incidence Mortality Newborn screening Outcome |
url |
http://link.springer.com/article/10.1186/s13023-017-0661-x |
work_keys_str_mv |
AT susannenettesheim incidencediseaseonsetandshorttermoutcomeinureacycledisorderscrossbordersurveillanceingermanyaustriaandswitzerland AT stefankolker incidencediseaseonsetandshorttermoutcomeinureacycledisorderscrossbordersurveillanceingermanyaustriaandswitzerland AT danielakarall incidencediseaseonsetandshorttermoutcomeinureacycledisorderscrossbordersurveillanceingermanyaustriaandswitzerland AT johanneshaberle incidencediseaseonsetandshorttermoutcomeinureacycledisorderscrossbordersurveillanceingermanyaustriaandswitzerland AT rolandposset incidencediseaseonsetandshorttermoutcomeinureacycledisorderscrossbordersurveillanceingermanyaustriaandswitzerland AT georgfhoffmann incidencediseaseonsetandshorttermoutcomeinureacycledisorderscrossbordersurveillanceingermanyaustriaandswitzerland AT beateheinrich incidencediseaseonsetandshorttermoutcomeinureacycledisorderscrossbordersurveillanceingermanyaustriaandswitzerland AT floriangleich incidencediseaseonsetandshorttermoutcomeinureacycledisorderscrossbordersurveillanceingermanyaustriaandswitzerland AT svenfgarbade incidencediseaseonsetandshorttermoutcomeinureacycledisorderscrossbordersurveillanceingermanyaustriaandswitzerland AT onbehalfofarbeitsgemeinschaftfurpadiatrischestoffwechselstorungenapseuropeanregistryandnetworkforintoxicationtypemetabolicdiseaseseimderhebungseinheitfurseltenepadiatrischeerkrankungenindeutschlandespedaustrianmetabolicgroupswisspaediatricsurveillanceunit incidencediseaseonsetandshorttermoutcomeinureacycledisorderscrossbordersurveillanceingermanyaustriaandswitzerland |
_version_ |
1726007451240628224 |
spelling |
doaj-23370ecb154343929b185a6fd10336132020-11-24T21:18:59ZengBMCOrphanet Journal of Rare Diseases1750-11722017-06-011211810.1186/s13023-017-0661-xIncidence, disease onset and short-term outcome in urea cycle disorders –cross-border surveillance in Germany, Austria and SwitzerlandSusanne Nettesheim0Stefan Kölker1Daniela Karall2Johannes Häberle3Roland Posset4Georg F. Hoffmann5Beate Heinrich6Florian Gleich7Sven F. Garbade8On behalf of Arbeitsgemeinschaft für Pädiatrische Stoffwechselstörungen (APS); European registry and network for Intoxication type Metabolic Diseases (E-IMD); Erhebungseinheit für Seltene Pädiatrische Erkrankungen in Deutschland (ESPED); Austrian Metabolic Group; Swiss Paediatric Surveillance Unit (SPSU)Division of Neuropediatrics and Metabolic Medicine, Center for Child and Adolescent Medicine, University Hospital HeidelbergDivision of Neuropediatrics and Metabolic Medicine, Center for Child and Adolescent Medicine, University Hospital HeidelbergMedical University of Innsbruck, Clinic for Pediatrics I, Inherited Metabolic DisordersUniversity Children’s Hospital Zurich, Division of Metabolism and Children’s Research CenterDivision of Neuropediatrics and Metabolic Medicine, Center for Child and Adolescent Medicine, University Hospital HeidelbergDivision of Neuropediatrics and Metabolic Medicine, Center for Child and Adolescent Medicine, University Hospital HeidelbergErhebungseinheit für Seltene Pädiatrische Erkrankungen in Deutschland, Coordination Center for Clinical Studies, Heinrich Heine University DüsseldorfDivision of Neuropediatrics and Metabolic Medicine, Center for Child and Adolescent Medicine, University Hospital HeidelbergDivision of Neuropediatrics and Metabolic Medicine, Center for Child and Adolescent Medicine, University Hospital HeidelbergAbstract 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.http://link.springer.com/article/10.1186/s13023-017-0661-xUrea cycle disorder(s)HyperammonemiaIncidenceMortalityNewborn screeningOutcome |