Format

Send to

Choose Destination
J Inherit Metab Dis. 2017 Jan;40(1):21-48. doi: 10.1007/s10545-016-9991-4. Epub 2016 Nov 30.

Guidelines for diagnosis and management of the cobalamin-related remethylation disorders cblC, cblD, cblE, cblF, cblG, cblJ and MTHFR deficiency.

Author information

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.
17
Newborn Screening, Metabolism & Genetics Unit, National Institute of Health, Porto, Portugal.
18
Section of Clinical Genetics and Metabolism, Department of Pediatrics, University of Colorado School of Medicine, Aurora, CO, USA.
19
Inherited Metabolic Diseases Clinic, Childrens Hospital Colorado, Aurora, CO, USA.
20
Institute of Inherited Metabolic Disorders, Charles University-First Faculty of Medicine and General University Hospital, Prague, Czech Republic.
21
Laboratory of Clinical Biochemistry and Metabolism, Center for Pediatrics and Adolescent Medicine University Hospital, Freiburg, Freiburg, Germany.
22
Division of Metabolism and Children's Research Center, University Childrens' Hospital Zürich, Zurich, Switzerland. matthias.baumgartner@kispi.uzh.ch.
23
radiz - Rare Disease Initiative Zürich, Clinical Research Priority Program, University of Zürich, Zurich, Switzerland. matthias.baumgartner@kispi.uzh.ch.
24
Division of Metabolism, Bambino Gesù Children's Research Hospital, Rome, Italy. carlo.dionisivici@opbg.net.

Abstract

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 experts on these rare diseases following the GRADE approach.

KEY RECOMMENDATIONS:

We strongly recommend measuring plasma total homocysteine in any patient presenting with the combination of neurological and/or visual and/or haematological symptoms, subacute spinal cord degeneration, atypical haemolytic uraemic syndrome or unexplained vascular thrombosis. We strongly recommend to initiate treatment with parenteral hydroxocobalamin without delay in any suspected remethylation disorder; it significantly improves survival and incidence of severe complications. We strongly recommend betaine treatment in individuals with MTHFR deficiency; it improves the outcome and prevents disease when given early.

PMID:
27905001
PMCID:
PMC5203859
DOI:
10.1007/s10545-016-9991-4
[Indexed for MEDLINE]
Free PMC Article

Conflict of interest statement

The authors of this guideline declare no competing interests but disclose the following: MRB has received financial support for attending E-HOD steering committee meetings from Orphan Europe. MRB and MH have received support from Milupa Metabolics for travel grants to develop a quality of life assessment tool for patients with intoxication type metabolic diseases. Charles University in Prague-First Faculty of Medicine received support from the Recordati Rare Disease Foundation for organizing an educational course on homocystinurias and methylation defects. MH, MRB, CDV, HB received speakers honoraria for their contribution to this educational course. The development of this guideline was part of the “European network and registry for homocystinurias and methylation defects (EHOD) project” (No.2012_12_02) which has received funding from the European Union in the framework of the Health Program. This article does not contain any studies with human or animal subjects performed by any of the authors.

Supplemental Content

Full text links

Icon for Wiley Icon for PubMed Central
Loading ...
Support Center