Overview of disorders and E-HOD Prof Henk Blom Coordinator E-HOD Clinical Biochemical Geneticist Laboratory for Clinical Biochemistry and Metabolism Department of General Pediatrics Center for Pediatrics and Adolescent Medicine University Hospital Freiburg, Germany

European Network and Registry for Homocystinurias and Methylation Disorders EAHC 2012 12 02 Henk Blom, coordinator

Disease panel Homocystinurias Methylation defects Folate defects CBS MTHFR CblC CblD CblE CblF CblG CblJ Methylation defects MAT GNMT SAHH ADK Folate defects MTHFD GFT FTCD

Homocysteine metabolism X AdoMet CH3-X Methionine AdoHcy THF Homocysteine 5,10-CH2-THF 5-MeTHF Cystathionine Cysteine simplified version

Homocysteine metabolism X AdoMet ATP MAT CH3-X Methionine AdoHcy THF Homocysteine 5,10-CH2-THF 5-MeTHF Cystathionine Cysteine MAT = methionine adenosyltransferase

Homocysteine metabolism X AdoMet methyltransferases CH3-X Methionine AdoHcy THF Homocysteine 5,10-CH2-THF 5-MeTHF Cystathionine Cysteine Methyltransfer is house-hold metabolism

DNA, RNA, proteins, lipids, neurotransmitters, etc. Homocysteine metabolism X AdoMet methyltransferases CH3-X Methionine AdoHcy DNA, RNA, proteins, lipids, neurotransmitters, etc. THF Homocysteine 5,10-CH2-THF 5-MeTHF Cystathionine Cysteine Methyltransfer is house-hold metabolism

Homocysteine metabolism X AdoMet CH3-X Methionine AdoHcy THF SAHH Homocysteine 5,10-CH2-THF 5-MeTHF Cystathionine Cysteine SAHH = S-adenosylhomocysteine hydrolase

Homocysteine converting enzymes X AdoMet CH3-X Methionine DNA, RNA, proteins, lipids, neurotransmitters, etc. B12 AdoHcy THF MS B2 Homocysteine MTHFR B6 5,10-CH2-THF 5-MeTHF CBS Cystathionine Cysteine THF = tetrahydrofolate, is also a B-vitamin

General objective E-HOD Promote health for children, adolescents and adults affecte with HCU and MD Reduce variation between countries Improve access to medical expertise and information for these rare diseases

Scope & objectives Improving knowledge on HCU and MD through collection of clinical data into a registry Developing diagnosis and clinical care recommendations Evaluating newborn screening (NBS) programme with recommendations European patient registry to describe the natural history, epidemiology, and current diagnostic and therapeutic strategies for homocystinurias and methylation defects; including data following patients picked up on NBS programmes To provide European evidence-based consensus care protocols for all diseases To evaluate the success rate of newborn screening programmes for homocystinuria with recommendations

Project structure WP4 Registry WP5 Guidelines WP6 Newborn screening Vertical WPs Horizontal WPs WP4 Registry WP lead: Heidelberg (Kölker)  All clinical beneficiaries and collaborating partners WP5 Guidelines WP lead: Rome (Dionisi-Vici)  All clinical beneficiaries and collaborating partners WP6 Newborn screening WP lead: Bregenz (Huemer) Experts from countries performing NBS WP1 Coordination WP lead: Freiburg (Blom) Advisory board, steering committee Synchronise with E-IMD WP2 Dissemination WP lead: Prague (Kozich)  Website, information leaflets, reports, posters WP3 Evaluation WP lead: Manchester (Morris)  External group including EUCERD, RD-Connect, JARD, PO members

E-HOD February 2013 13 associate partners 19 collaborating centers Coordinator Associate partners Collaborating partners E-IMD co-beneficiaries 13 associate partners 19 collaborating centers From 15 countries 2 patient support groups UNIMAN VUmc CUH UMCR CUNI UKL-HD APHP OE FFUL CIBERER OPBG UZMS Doha, Qatar LKHB

75 clinical collaborating partners 7 other collaborating partners The network has expanded from 32 partners (13 associated and 19 collaborating) in 15 European countries to a group of 62 partners (an additional 30 collaborating partners) in 25 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. 13 associated partners 75 clinical collaborating partners 7 other collaborating partners from 28 countries

Patient registry: Participating centers: 63 Patients registered:    493

Current activities Guidelines on CBS, remethylation and methylation Training course, Prague, March 2016 First Patient-Expert Meeting Prague, February 29, 2016 Continous support collaborating partners to obtain ethical approval for the registry, see https://www.ehod-registry.org Continuating communication and dissemination, see http://www.e-hod.org

Professionals (care givers, researchers) E-HOD Public-private partnerships Patient organisations

Professionals (care givers, researchers) E-HOD Public-private partnerships Patient organisations

E-HOD Network Professionals E-HOD Public-private partnerships Patient organisations

E-HOD would like to thank Public-private partnerships Professionals Patient organizations European Union Patient Organisations All Patients and their families Collaborating partners Thank you all!

Thank you for your attention, Greetings from Freiburg!

Public-private partnerships Professionals Patient organizations

Folic acid and vascular disease: a tale with two faces? Good: not using antiplatelet agents? Bad: if on antiplatelet agents? Irena Shklover

Contract number: EAHC 2012 12 02 Starting date: 15th February 2013 Duration of the project: 39 months Total amount of the project: €1.151.870 € 690.793