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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


Posset, Roland; Garbade, Sven F; Boy, Nikolas; Burlina, Alberto B; Dionisi-Vici, Carlo; Dobbelaere, Dries; Garcia-Cazorla, Angeles; de Lonlay, Pascale; Teles, Elisa Leão; Vara, Roshni; Ah Mew, Nicholas; Batshaw, Mark L; Baumgartner, Matthias R; McCandless, Shawn; Seminara, Jennifer; Summar, Marshall; Hoffmann, Georg F; Kölker, Stefan; Burgard, Peter (2018). 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:Epub ahead of print.

Abstract

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 utilising differences in approach to treatment can evaluate therapeutic options and enhance long-term outcome studies.

Abstract

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 utilising differences in approach to treatment can evaluate therapeutic options and enhance long-term outcome studies.

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Additional indexing

Contributors:Additional individual contributors of the UCDC and the E-IMD consortium
Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Children's Hospital Zurich > Medical Clinic
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:4 July 2018
Deposited On:11 Jan 2019 10:11
Last Modified:25 Sep 2019 00:01
Publisher:Springer
ISSN:0141-8955
OA Status:Closed
Publisher DOI:https://doi.org/10.1007/s10545-018-0222-z
PubMed ID:29974348

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