TY - JOUR
T1 - Transatlantic combined and comparative data analysis of 1095 patients with urea cycle disorders—A successful strategy for clinical research of rare diseases
AU - Additional Individual Contributors Of The Ucdc And The E-Imd Consortium
AU - Posset, Roland
AU - Garbade, Sven F.
AU - Boy, Nikolas
AU - Burlina, Alberto B.
AU - Dionisi-Vici, Carlo
AU - Dobbelaere, Dries
AU - Garcia-Cazorla, Angeles
AU - de Lonlay, Pascale
AU - Teles, Elisa Leão
AU - Vara, Roshni
AU - Mew, Nicholas Ah
AU - Batshaw, Mark L.
AU - Baumgartner, Matthias R.
AU - McCandless, Shawn E.
AU - Seminara, Jennifer
AU - Summar, Marshall
AU - Hoffmann, Georg F.
AU - Kölker, Stefan
AU - Burgard, Peter
AU - Burrage, Lindsay
AU - Coughlin, Curtis
AU - Diaz, George A.
AU - Gallagher, Renata C.
AU - Gropman, Andrea
AU - Harding, Cary O.
AU - Lee, Brendan
AU - Berry, Susan A
AU - Lawrence Merritt, J.
AU - Nagamani, Sandesh C.S.
AU - Schulze, Andreas
AU - Stricker, Tamar
AU - Tuchman, Mendel
AU - Waisbren, Susan
AU - WeisfeldAdams, James
AU - Wong, Derek
AU - Yudkoff, Marc
AU - Arnoux, Jean Baptiste
AU - Barić, Ivo
AU - Bosch, Annet M.
AU - Chabrol, Brigitte
AU - Chakrapani, Anupam
AU - CortèsSaladefont, Elisenda
AU - Couce, Maria L.
AU - Eyskens, Francois
AU - de Laet, Corine
AU - de Meirleir, Linda
AU - Freisinger, Peter
AU - Gleich, Florian
AU - Grünewald, Stephanie
N1 - Publisher Copyright:
© 2018 SSIEM
PY - 2019/1
Y1 - 2019/1
N2 - Background: To improve our understanding of urea cycle disorders (UCDs) prospectively followed by two North American (NA) and European (EU) patient cohorts. Aims: Description of the NA and EU patient samples and investigation of the prospects of combined and comparative analyses for individuals with UCDs. Methods: Retrieval and comparison of the data from 1095 individuals (NA: 620, EU: 475) from two electronic databases. Results: The proportion of females with ornithine transcarbamylase deficiency (fOTC-D), particularly those being asymptomatic (asfOTC-D), was higher in the NA than in the EU sample. Exclusion of asfOTC-D resulted in similar distributions in both samples. The mean age at first symptoms was higher in NA than in EU patients with late onset (LO), but similar for those with early (≤ 28 days) onset (EO) of symptoms. Also, the mean age at diagnosis and diagnostic delay for EO and LO patients were similar in the NA and EU cohorts. In most patients (including fOTC-D), diagnosis was made after the onset of symptoms (59.9%) or by high-risk family screening (24.7%), and less often by newborn screening (8.9%) and prenatal testing (3.7%). Analysis of clinical phenotypes revealed that EO patients presented with more symptoms than LO individuals, but that numbers of symptoms correlated with plasma ammonium concentrations in EO patients only. Liver transplantation was reported for 90 NA and 25 EU patients. Conclusions: Combined analysis of databases drawn from distinct populations opens the possibility to increase sample sizes for natural history questions, while comparative analysis utilizing differences in approach to treatment can evaluate therapeutic options and enhance long-term outcome studies.
AB - Background: To improve our understanding of urea cycle disorders (UCDs) prospectively followed by two North American (NA) and European (EU) patient cohorts. Aims: Description of the NA and EU patient samples and investigation of the prospects of combined and comparative analyses for individuals with UCDs. Methods: Retrieval and comparison of the data from 1095 individuals (NA: 620, EU: 475) from two electronic databases. Results: The proportion of females with ornithine transcarbamylase deficiency (fOTC-D), particularly those being asymptomatic (asfOTC-D), was higher in the NA than in the EU sample. Exclusion of asfOTC-D resulted in similar distributions in both samples. The mean age at first symptoms was higher in NA than in EU patients with late onset (LO), but similar for those with early (≤ 28 days) onset (EO) of symptoms. Also, the mean age at diagnosis and diagnostic delay for EO and LO patients were similar in the NA and EU cohorts. In most patients (including fOTC-D), diagnosis was made after the onset of symptoms (59.9%) or by high-risk family screening (24.7%), and less often by newborn screening (8.9%) and prenatal testing (3.7%). Analysis of clinical phenotypes revealed that EO patients presented with more symptoms than LO individuals, but that numbers of symptoms correlated with plasma ammonium concentrations in EO patients only. Liver transplantation was reported for 90 NA and 25 EU patients. Conclusions: Combined analysis of databases drawn from distinct populations opens the possibility to increase sample sizes for natural history questions, while comparative analysis utilizing differences in approach to treatment can evaluate therapeutic options and enhance long-term outcome studies.
KW - Urea cycle Disorders
KW - diagnostic methods
KW - international registry and database
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U2 - 10.1002/jimd.12031
DO - 10.1002/jimd.12031
M3 - Article
C2 - 30740724
AN - SCOPUS:85061242211
SN - 0141-8955
VL - 42
SP - 93
EP - 106
JO - Journal of Inherited Metabolic Disease
JF - Journal of Inherited Metabolic Disease
IS - 1
ER -