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

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 sym