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Transatlantic combined and comparative data analysis of 1095 patients with urea cycle disorders-A successful strategy for clinical research of rare diseases

Authors :
Posset, Roland
Garbade, Sven F.
Boy, Nikolas
Burlina, Alberto B.
Dionisi-Vici, Carlo
Dobbelaere, Dries
Garcia-Cazorla, Angeles
de Lonlay, Pascale
Teles, Elisa Leao
Vara, Roshni
Mew, Nicholas Ah.
Batshaw, Mark L.
Baumgartner, Matthias R.
McCandless, Shawn
Seminara, Jennifer
Summar, Marshall
Hoffmann, Georg F.
Koelker, Stefan
Burgard, Peter
Bloxam, Sondra
Brody, Linnea
Caspi, Liora
Elsbecker, Sara
Fierro, Luca
Lynn, Audrey
Mullins, Mary
Mutze, Ulrike
Papaleo, Cassandra
Payan, Irma
Simpson, Kara
Singer, Rebecca
Wallis, Kimberly
Alber, Fabienne Dietrich
Babikian, Talin
Bender, Heidi
Boys, Christopher
Breiger, David
Buerger, Corinna
Caudle, Susan E.
Nguyen-Driver, Mina
Kerr, Elizabeth
Mamak, Eva
Sanz, Jacqueline H.
Tangen, Rachel
Wilkening, Greta
Cederbaum, Stephen
Feigenbaum, Annette
Kerr, Douglas S.
Lichter-Konecki, Uta
Seashore, Margretta R.
Berry, Susan A.
Burrage, Lindsay
Coughlin, Curtis
Diaz, George A.
Gallagher, Renata C.
Gropman, Andrea
Harding, Cary O.
Lee, Brendan
Le Mons, Cynthia
Merritt, J. Lawrence, II
Nagamani, Sandesh C. S.
Schulze, Andreas
Stricker, Tamar
Tuchman, Mendel
Waisbren, Susan
Weisfeld-Adams, James
Wong, Derek
Yudkoff, Marc
Arnoux, Jean-Baptiste
Baric, Ivo
Bosch, Annet M.
Chabrol, Brigitte
Chakrapani, Anupam
Cortes-Saladefont, Elisenda
Couce, Maria L.
Eyskens, François
de Laet, Corine
de Meirleir, Linda
Freisinger, Peter
Gleich, Florian
Grunewald, Stephanie
Haberle, Johannes
Hwu, Wuh-Liang
Jalan, Anil
Karall, Daniela
Lindner, Martin
Lund, Allan M.
Martinelli, Diego
Murphy, Elaine
Muehlhausen, Chris
Olivieri, Giorgia
Ottolenghi, Chris
Rodrigues, Esmeralda
Rubert, Laura
Sarajlija, Adrijan
Schiff, Manuel
Sokal, Etienne
Sykut-Cegielska, Jolanta
Walter, John H.
Williams, Monique
Zeman, Jiri
Pediatric surgery
Clinical chemistry
AGEM - Endocrinology, metabolism and nutrition
AGEM - Inborn errors of metabolism
Amsterdam Reproduction & Development (AR&D)
Pediatrics
Paediatric Metabolic Diseases
University of Zurich
Burgard, Peter
UCL - SSS/IREC/PEDI - Pôle de Pédiatrie
UCL - (SLuc) Service de gastro-entérologie et hépatologie pédiatrique
UCDC
E-IMD Consortium
Source :
Journal of inherited metabolic disease, vol 42, iss 1, Journal of Inherited Metabolic Disease, 42(1), 93-106. Springer Netherlands, Posset, R, Garbade, S F, Boy, N, Burlina, A B, Dionisi-Vici, C, Dobbelaere, D, Garcia-Cazorla, A, de Lonlay, P, Teles, E L, Vara, R, Mew, N A, Batshaw, M L, Baumgartner, M R, McCandless, S E, Seminara, J, Summar, M, Hoffmann, G F, Kölker, S, Burgard, P, Additional individual contributors of the UCDC and the E-IMD consortium & Zeman, J 2019, ' Transatlantic combined and comparative data analysis of 1095 patients with urea cycle disorders—A successful strategy for clinical research of rare diseases ', Journal of Inherited Metabolic Disease, vol. 42, no. 1, pp. 93-106 . https://doi.org/10.1002/jimd.12031, Journal of inherited metabolic disease, 42(1), 93-106. Springer Netherlands, J Inherit Metab Dis, Journal of Inherited Metabolic Disease, Vol. 42, no. 1, p. 93-106 (2019), Journal of inherited metabolic disease
Publication Year :
2019
Publisher :
eScholarship, University of California, 2019.

Abstract

ollaborators: Bloxam S, Brody L, Caspi L, Elsbecker S, Fierro L, Lynn A, Mullins M, Mütze U, Papaleo C, Payan I, Seminara J, Simpson K, Singer R, Wallis K, Alber FD, Babikian T, Bender H, Boys C, Breiger D, Buerger C, Caudle SE, NguyenDriver M, Kerr E, Mamak E, Sanz JH, Tangen R, Wilkening G, Cederbaum S, Feigenbaum A, Kerr DS, LichterKonecki U, Seashore MR, Berry SA, Burrage L, Coughlin C, Diaz GA, Gallagher RC, Gropman A, Harding CO, Lee B, Le Mons C, Lawrence Merritt J 2nd, Nagamani SCS, Schulze A, Stricker T, Tuchman M, Waisbren S, WeisfeldAdams J, Wong D, Yudkoff M, Arnoux J, Bari Cacute I, Bosch AM, Chabrol B, Chakrapani A, CortèsSaladefont E, Couce ML, Eyskens F, de Laet C, de Meirleir L, Freisinger P, Gleich F, Grünewald S, Häberle J, Hwu W, Jalan A, Karall D, Lindner M, Lund AM, Martinelli D, Murphy E, Mühlhausen C, Olivieri G, Ottolenghi C, Rodrigues E, Rubert L, Sarajlija A, Schiff M, Sokal E, SykutCegielska J, Walter JH, Williams M, Zeman J. 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.

Details

ISSN :
01418955
Database :
OpenAIRE
Journal :
Journal of inherited metabolic disease, vol 42, iss 1, Journal of Inherited Metabolic Disease, 42(1), 93-106. Springer Netherlands, Posset, R, Garbade, S F, Boy, N, Burlina, A B, Dionisi-Vici, C, Dobbelaere, D, Garcia-Cazorla, A, de Lonlay, P, Teles, E L, Vara, R, Mew, N A, Batshaw, M L, Baumgartner, M R, McCandless, S E, Seminara, J, Summar, M, Hoffmann, G F, Kölker, S, Burgard, P, Additional individual contributors of the UCDC and the E-IMD consortium & Zeman, J 2019, ' Transatlantic combined and comparative data analysis of 1095 patients with urea cycle disorders—A successful strategy for clinical research of rare diseases ', Journal of Inherited Metabolic Disease, vol. 42, no. 1, pp. 93-106 . https://doi.org/10.1002/jimd.12031, Journal of inherited metabolic disease, 42(1), 93-106. Springer Netherlands, J Inherit Metab Dis, Journal of Inherited Metabolic Disease, Vol. 42, no. 1, p. 93-106 (2019), Journal of inherited metabolic disease
Accession number :
edsair.doi.dedup.....d93d4609396aef463719272a84cbaf6b