Overview of disorders and EHOD Prof Henk Blom

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 • • CBS MTHFR Cbl. C Cbl. D Cbl. E Cbl. F Cbl. G Cbl. J Methylation defects • • MAT GNMT SAHH ADK Folate defects • • • MTHFD GFT FTCD

Homocysteine metabolism X Ado. Met CH 3 -X Methionine Ado. Hcy THF Homocysteine 5, 10 -CH 2 -THF 5 -Me. THF Cystathionine Cysteine simplified version

Homocysteine metabolism X Ado. Met ATP MAT Methionine CH 3 -X Ado. Hcy THF Homocysteine 5, 10 -CH 2 -THF 5 -Me. THF Cystathionine Cysteine MAT = methionine adenosyltransferase

Homocysteine metabolism X Ado. Met methyltransferases CH 3 -X Methionine Ado. Hcy THF Homocysteine 5, 10 -CH 2 -THF 5 -Me. THF Cystathionine Cysteine Methyltransfer is house-hold metabolism

Homocysteine metabolism X Ado. Met methyltransferases CH 3 -X Methionine Ado. Hcy THF Homocysteine 5, 10 -CH 2 -THF 5 -Me. THF Cystathionine Cysteine Methyltransfer is house-hold metabolism DNA, RNA, proteins, lipids, neurotransmitters, etc.

Homocysteine metabolism X Ado. Met CH 3 -X Methionine Ado. Hcy THF SAHH Homocysteine 5, 10 -CH 2 -THF 5 -Me. THF Cystathionine Cysteine SAHH = S-adenosylhomocysteine hydrolase

Homocysteine converting enzymes X Ado. Met CH 3 -X Methionine B 12 THF Ado. Hcy MS B 2 5, 10 -CH 2 -THF MTHFR Homocysteine 5 -Me. THF CBS B 6 Cystathionine THF = tetrahydrofolate, is also a B-vitamin Cysteine DNA, RNA, proteins, lipids, neurotransmitters, etc.

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

Project structure Horizontal WPs Vertical WPs WP 1 Coordination WP lead: Freiburg (Blom) Advisory board, steering committee Synchronise with E-IMD WP 2 Dissemination WP lead: Prague (Kozich) Website, information leaflets, reports, posters WP 3 Evaluation WP lead: Manchester (Morris) External group including EUCERD, RD-Connect, JARD, PO members WP 4 Registry WP 5 Guidelines WP lead: Heidelberg (Kölker) All clinical beneficiaries and collaborating partners WP lead: Rome (Dionisi-Vici) All clinical beneficiaries and collaborating partners WP 6 Newborn screening WP lead: Bregenz (Huemer) Experts from countries performing NBS

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

13 associated partners 75 clinical collaborating partners 7 other collaborating partners from 28 countries

Patient registry: Participating centers: 63 Patients registered: 493

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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. ehodregistry. org - Continuating communication and dissemination, see http: //www. e-hod. org

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

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

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

Thank you for your attention, Greetings from Freiburg!

Professionals Patient organizations Public-private partnerships

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: 15 th February 2013 Duration of the project: 39 months Total amount of the project: € 1. 151. 870 € 690. 793