First annual activity report

EXECUTIVE SUMMARY

Homocystinurias (HCU), methylation (MD) and folate defects (FD) are groups of rare chronic severe intoxication type inborn errors of metabolism (IEM) with overlapping phenotype. Individuals may present in infancy and risk reduced quality of life and life expectancy. A major problem facing these rare diseases (RD) is that no single centre, and in many cases no single country, has sufficient numbers of patients and resources to fully understand the natural history or to conduct clinical and translational research. There are no evidence-based guidelines and there are differences, between member states in infrastructure, expertise, time to diagnosis, treatment and outcome. In only seven member states (MS) newborn screening (NBS) for HCU due to Cystathionine β-Synthase (CBS) deficiency is performed. Therefore the pooling of manpower and resources through the establishment of a network and a registry is indispensable to improve the knowledge base, to develop European consensus guidelines and to foster networking on a European level.

 

SCOPE AND OBJECTIVES

The overall aim of the network and registry for homocystinurias and methylation defects (E-HOD) is to promote health for children, adolescents and adults affected with these rare and severe diseases. There are three specific objectives:

  1. improving knowledge on homocystinurias (HCU) and methylation defects (MD) through the collection of clinical data into a registry,
  2. developing diagnosis and clinical care recommendations,
  3. evaluating the newborn screening (NBS) programme with recommendations.

 

WORK ACHIEVED IN THE FIRST 12 MONTHS

The network has expanded from 32 partners (13 associated and 19 collaborating) in 15 European countries to a group of 49 partners (an additional 17 collaborating partners) in 24 countries. The network includes clinicians, scientists, dietitians, patient organisations and industry representatives. Representatives of other consortia have become members of E-HOD including those of the SSIEM adult metabolic group, the SSIEM dietitians’ group thereby linking E-HOD with other organisations dedicating to improved health for patients with rare UCDs and OADs.

The registry has achieved ethical approval in 19 centres and 93 patients have been registered

The web-site has received 2,250 unique visitors, over the first 5 months, who spend an average of 29 minutes on the website. We receive requests for advice about individual patients. Contacts through the web are rapidly put in touch with one of our network members in that country or at least the requests are replied in the patient’s own language. A combination of publications, web links and oral & poster presentations mentioning E-HOD has been initiated.

International guideline development groups have been set-up. Over 1000 publications have been searched and classified according to each group and subtopic. Partners evaluate each publication using a Monkey Survey questionnaire according to SIGN methodology. E-HOD has defined 4 groups for the guidelines:

  1. Classical homocystinurias/CBS deficiency
  2. Cobalamin defects
  3. Methylation defects and other related disorders (MAT I/III, GNMT, SAHH, ADK)
  4. Newborn screening evaluation group   

 

CONCLUSIONS

E-HOD has achieved all milestones and deliverables for this first period. The project is innovative as it adds value to the reflection on EU Reference Networks and registries clustering 15 RD onto an existing network and registry (E-IMD) of 11 intoxication type diseases (E-IMD is funded by the EC EAHC 2010 12 01). It also adds value to the reflection on NBS programmes. Following the EMA/EUCERD discussions on the need to develop a unique source of data by disease, E-HOD leads the way in building a registry, with improved sustainability, for researchers, regulators, payers and for orphan drug follow-up through a strategy to develop public/private partnerships. Given the particularly low number of patients and the complexity of the diseases, no national or regional project in Europe would be able to perform this work.

 

Acknowledgements

 

E-HOD would like to thank:

  • The European Union, in the framework of the Health Programme (2008-2013) for funding and support.
  • Patient organisations that serve the network and give their time.
  • All patients and their families – for their important collaboration and for their trust in E-HOD.
  • Collaborating partners who serve the network and give their time. 

The full Annual Activity Report can be downloaded HERE.