Networking Across Borders for Individuals with Organic Acidurias and Urea Cycle Disorders: The E-IMD Consortium

Abstract

Background: Patients with organic acidurias (OAD) and urea cycle disorders (UCD) are at increased risk of disability, impaired quality of life and reduced life expectancy. Clinical care in any one centre is constrained by small patient numbers; and furthermore diagnostic and treatment strategies vary between metabolic centres and countries, resulting in significant inequalities and disparity in patient outcome. Aims/methods:The overall objective of the EU-funded activity 'European registry and network for intoxication type metabolic diseases' (E-IMD) is to collect systematic data to improve the knowledge of these diseases, to develop consensus care guidelines and to provide detailed information materials for families and professionals.Results: Within three years E-IMD has (1) established a network of 87 partners in 25 countries (2) set up a patient registry of more than 1,000 individuals with OAD and UCD, (3) launched a website (www.e-imd.org) including detailed information materials in 11 languages, (4) developed guidelines for OAD and UCD, (5) organised two teaching courses and various scientific meetings, (6) extended the IT platform clustering with other inherited metabolic diseases (IMD) and (7) strengthened the collaboration with other international scientific consortia.Conclusions: E-IMD has made important steps towards improving and sharing knowledge on OAD and UCD and harmonisation of diagnostic and therapeutic strategies. Through the establishment of a modular patient registry, clustering with other IMD and stepwise extension of the network, E-IMD has implemented the core components of a European Reference Network for rare diseases. Abbreviations

The phenotypic spectrum of organic acidurias and urea cycle disorders. Part 1: the initial presentation

“…Since newborn screening programmes for OAD and UCD have so far been established in a few European countries Loeber et al 2012) and symptomatic patients might be missed for various reasons, it is quite likely that the E-IMD dataset is skewed and under-represents patients with a severe phenotype to some extent. In line with this, we previously demonstrated that estimated minimum prevalences for OAD and UCD varied in different countries (Kölker et al 2015). Furthermore, the geographic distribution of rare diseases is variable and relies on genetic differences in populations such as localized founder effects.…”

“…It has been realized without industrial sponsoring. A detailed description of E-IMD will be published separately (Kölker et al 2015).…”

Early prediction of phenotypic severity in Citrullinemia Type 1

“…Large observational natural history studies of UCDs in North America [Urea Cycle Disorders Consortium (UCDC; https://www.rarediseasesnetwork.org/cms/ucdc)] and Europe [European registry and network for intoxication type metabolic disease (E‐IMD; https://www.eimd-registry.org/)] have identified clinical variables, such as early disease onset, or biochemical variables, such as high initial peak plasma ammonium concentration (NH 4 + max ), to be correlated with poor long‐term outcome . However, phenotypic severity has not been predictable early during the disease course so far.…”

Impact of Diagnosis and Therapy on Cognitive Function in Urea Cycle Disorders

“…However, there is still uncertainty about the benefit of NBS for individuals with ASS1-D and ASL-D, diseases that are rarely included in NBS disease panels in Europe but more commonly in the United States. [14][15][16] Although recent studies from both consortia have significantly improved our understanding of the natural history of UCDs, the impact of early diagnosis (by NBS) and long-term scavenger treatment on the overall neurocognitive outcome is still unclear. 11 Previous studies have highlighted that disease onset (EO vs LO), initial peak plasma ammonium concentration (NH 4 + max ), duration of hyperammonemic episodes, and hyperammonemic encephalopathy with coma are among the best predictors of mortality and severity of the neurological impairment.…”

“…[2][3][4]12,13 Large international registry studies from North America (the Urea Cycle Disorders Consortium [UCDC], https:// www.rarediseasesnetwork.org/cms/ucdc, activated in February 2006) and from Europe (the European Registry and Network for Intoxication Type Metabolic Diseases [E-IMD], https:// www.eimd-registry.org/, activated in January 2011) have been systematically collecting comprehensive longitudinal clinical, neurological, biochemical, and therapy-related data. [14][15][16] Although recent studies from both consortia have significantly improved our understanding of the natural history of UCDs, the impact of early diagnosis (by NBS) and long-term scavenger treatment on the overall neurocognitive outcome is still unclear. 13 Therefore, we compared and combined data from the UCDC and E-IMD registries to increase statistical power and investigated the largest cohort worldwide consisting of 1,095 individuals with UCDs.…”