Guidelines for diagnosis and management... cblF, cblG, cblJ and MTHFR deficiency

Background Remethylation defects are rare inherited disorders in which impaired remethylation of homocysteine to methionine leads to accumulation of homocysteine and perturbation of numerous methylation reactions. Objective To summarise clinical and biochemical characteristics of these severe disorders and to provide guidelines on diagnosis and management. Data sources Review, evaluation and discussion of the medical literature (Medline, Cochrane databases) by a panel of Commnunicated by: Sylvia Stoeckler-Ipsiroglu Martina Huemer, Daria Diodato, Matthias R. Baumgartner and Carlo Dionisi-Vici contributed equally to this work. Electronic supplementary material The online version of this article (doi:10.1007/s10545-016-9991-4) contains supplementary material, which is available to authorised users. * Matthias R. Baumgartner matthias.baumgartner@kispi.uzh.ch * Carlo Dionisi-Vici carlo.dionisivici@opbg.net 1 Division of Metabolism and Children’s Research Center, University Childrens’ Hospital Zürich, Zurich, Switzerland 2 radiz – Rare Disease Initiative Zürich, Clinical Research Priority Program, University of Zürich, Zurich, Switzerland 3 Department of Paediatrics, Landeskrankenhaus Bregenz, Bregenz, Austria 4 Division of Metabolism, Bambino Gesù Children’s Research Hospital, Rome, Italy 5 Willink Biochemical Genetics Unit, Saint Mary’s Hospital, Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester M13 9WL, UK 6 Reference Center for Inborn Errors of Metabolism, Robert Debré University Hospital, APHP, Paris, France 7 Inserm U1141, Robert Debré Hospital, Paris, France 8 Université Paris-Diderot, Sorbonne Paris Cité, site Robert Debré, Paris, France 9 Metabolic Unit, Centro Hospitalar do Porto, Porto, Portugal 10 Biochimie, faculté de pharmacie, Université Paris Sud, Paris, France 11 Division of Inherited Metabolic Diseases, Department of Pediatrics, University Hospital Padova, Padova, Italy 12 University Dept of Pediatrics, Giannina Gaslini Institute, Genoa, Italy 13 Congenital Metabolic Diseases Unit, Hospital Clínico Universitario de Santiago de Compostela, IDIS, CIBER, Compostela, Spain 14 Department of Neurology, Neurometabolism Unit, and CIBERER (ISCIII), Hospital Sant Joan de Deu, Barcelona, Spain 15 Department of Experimental and Clinical Biomedical Sciences, University of Florence, Firence, Italy 16 Metabolic and Newborn Screening Clinical Unit, Department of Neurosciences, A. Meyer Children’s University Hospital, Florence, Italy J Inherit Metab Dis (2017) 40:21–48 DOI 10.1007/s10545-016-9991-4