Journal article
Phenotype, treatment practice and outcome in the cobalamin-dependent remethylation disorders and MTHFR deficiency: Data from the E-HOD registry.
- Huemer M Division of Metabolism and Children's Research Center, University Children's Hospital, Zürich, Switzerland.
- Diodato D Division of Metabolism, Bambino Gesù Children's Hospital, Rome, Italy.
- Martinelli D Division of Metabolism, Bambino Gesù Children's Hospital, Rome, Italy.
- Olivieri G Division of Metabolism, Bambino Gesù Children's Hospital, Rome, Italy.
- Blom H Department of Internal Medicine, VU Medical Center, Amsterdam, The Netherlands.
- Gleich F Division of Child Neurology and Metabolic Medicine, Centre for Child and Adolescent Medicine, Heidelberg, Germany.
- Kölker S Division of Child Neurology and Metabolic Medicine, Centre for Child and Adolescent Medicine, Heidelberg, Germany.
- Kožich V Department of Pediatrics and Adolescent Medicine, Charles University-First Faculty of Medicine and General University Hospital, Prague, Czech Republic.
- Morris AA Willink Metabolic Unit, Genomic Medicine, Manchester University Hospitals NHS Foundation Trust, Manchester, UK.
- Seifert B Department of Biostatistics at Epidemiology, Biostatistics and Prevention Institute, University Zürich, Zürich, Switzerland.
- Froese DS Division of Metabolism and Children's Research Center, University Children's Hospital, Zürich, Switzerland.
- Baumgartner MR Division of Metabolism and Children's Research Center, University Children's Hospital, Zürich, Switzerland.
- Dionisi-Vici C Division of Metabolism, Bambino Gesù Children's Hospital, Rome, Italy.
- Martin CA Department of Pediatrics, Sozialpädiatrisches Zentrum, Klinikum Dritter Orden München-Nymphenburg, Munich, Germany.
- Baethmann M Center for Molecular Diseases, University Hospital Lausanne, Lausanne, Switzerland.
- Ballhausen D Sección de Gastroenterología y Nutrición Pediátrica, Hospital Regional de Málaga, Málaga, Spain.
- Blasco-Alonso J Division of Child Neurology and Metabolic Medicine, Centre for Child and Adolescent Medicine, Heidelberg, Germany.
- Boy N Hospital Universitario Virgen del Rocío, Sevilla, Spain.
- Bueno M Nutritional Support Unit, University Hospital Vall d'Hebron, Barcelona, Spain.
- Burgos Peláez R University Department of Pediatrics, Giannina Gaslini Institute, Genoa, Italy.
- Cerone R Centre de Référence des Maladies Héréditaires du Métabolisme, CHU La Timone Enfants, Marseille, France.
- Chabrol B Children's National Rare Disease Institute, Genetics and Metabolism, Washington, DC, USA.
- Chapman KA Unit of Diagnosis and Treatment of Congenital Metabolic Diseases, Service of Neonatology, Department of PediatricsHospital Clínico Universitario de Santiago, CIBERER, Health Research Institute of Santiago de Compostela (IDIS), Santiago de Compostela, Spain.
- Couce ML National Centre for Inherited Metabolic Disorders, Temple Street Children's University Hospital, Dublin, Ireland.
- Crushell E Unidad de Nutrición y Metabolopatías, Hospital Universitario La Fe, Valencia, Spain.
- Dalmau Serra J Centro de Referência de Doencas Hereditárias do Metabolismo. Centro de Desenvolvimento da Criança - Hospital Pediátrico - Centro Hospitalar e Universitário De Coimbra, Coimbra, Portugal.
- Diogo L Division of Human Genetics, The Children's Hospital of Philadelphia, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania.
- Ficicioglu C Hospital Infantil Miguel Servet, Zaragoza, Spain.
- García Jimenez MC Universitary Hospital 12 Octubre, Madrid, Spain.
- García Silva MT Centro Academico de Medicina de Lisboa, Lisbon, Portugal.
- Gaspar AM Interdisciplinary Metabolic Team, Paediatric Endocrinology, Diabetology and Metabolism, University Children's Hospital and University Institute of Clinical Chemistry Inselspital, Berne, Switzerland.
- Gautschi M Department of Pediatrics, University Hospital Marqués de Valdecilla, Universidad de Cantabria, Santander, Spain.
- González-Lamuño D Unit of Diagnosis and Treatment of Congenital Metabolic Diseases, Service of Neonatology, Department of PediatricsHospital Clínico Universitario de Santiago, CIBERER, Health Research Institute of Santiago de Compostela (IDIS), Santiago de Compostela, Spain.
- Gouveia S Institute for Child HealthGreat Ormond Street Hospital, University College London, London, UK.
- Grünewald S Salford Royal NHS Foundation Trust, Salford, UK.
- Hendriksz C Department of Internal Medicine, Radboud University Medical Center, Nijmegen, The Netherlands.
- Janssen MCH Department of Pediatrics and Adolescent Medicine, Charles University-First Faculty of Medicine and General University Hospital, Prague, Czech Republic.
- Jesina P Department of Pediatrics, Salzburger Landeskliniken and Paracelsus Medical University, Salzburg, Austria.
- Koch J Department of Pediatrics and Adolescent Medicine, Medical University Vienna, Vienna, Austria.
- Konstantopoulou V Médecine Interne et Maladies Vasculaires, Centre Hospitalier Universitaire Angers, Angers, France.
- Lavigne C Centre Inherited Metabolic Diseases, Departments of Clinical Genetics and Paediatrics, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
- Lund AM Reference Center for Inherited Metabolic Diseases, Centro Hospitalar do Porto, Porto, Portugal.
- Martins EG Division of Gastroenterology, Hepatology and Nutrition, Sant Joan de Déu Hospital, Barcelona, Spain.
- Meavilla Olivas S Hôpital Jeanne de Flandre, Lille, France.
- Mention K Reference Center for Adult Neurometabolic Diseases, University Pierre and Marie Curie, La Pitié-Salpêtrière University Hospital, Paris, France.
- Mochel F Evelina London Children's Hospital, London, UK.
- Mundy H Charles Dent Metabolic Unit, National Hospital for Neurology and Neurosurgery, London, UK.
- Murphy E Pediatric Neurology and Metabolic diseases department, Université Catholique de Louvain, Cliniques Universitaires Saint-Luc, Brussels, Belgium.
- Paquay S Division of Gastroenterology and Nutrition, University Children's Hospital Niño Jesús, Madrid, Spain.
- Pedrón-Giner C Metabolic Neuropediatric Unit, University Hospital Son Espases, Palma de Mallorca, Spain.
- Ruiz Gómez MA Clinical Inherited Metabolic Disorders, Birmingham Women's and Children's NHS Foundation Trust, Birmingham, UK.
- Santra S Reference Center for Inherited Metabolic Diseases, AP-HP, Robert Debré Hospital, University Paris Diderot-Sorbonne Paris Cité and INSERM U1141, Paris, France.
- Schiff M Hospital de Clínicas de Porto Alegre and Department of Genetics, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
- Schwartz IV Clinic for Pediatrics I, Inherited Metabolic Disorders Medical University of Innsbruck, Innsbruck, Austria.
- Scholl-Bürgi S Nephrology Department, Reference Center of Inherited Metabolic Diseases, Necker hospital, AP-HP, University Paris Descartes, Paris, France.
- Servais A Agia Sofia Children's Hospital 1st Department of Pediatrics, University of Athens Thivon & Levadias, Athens, Greece.
- Skouma A Center for Molecular Diseases, University Hospital Lausanne, Lausanne, Switzerland.
- Tran C Hospital Universitario Virgen de la Arrixaca, El Palmar, Spain.
- Vives Piñera I Willink Metabolic Unit, Genomic Medicine, Manchester University Hospitals NHS Foundation Trust, Manchester, UK.
- Walter J Inherited Metabolic Diseases Clinic, Section of Clinical Genetics and Metabolism, University of Colorado Denver, Aurora, Colorado.
- Weisfeld-Adams J
- 2019-02-19
Published in:
- Journal of inherited metabolic disease. - 2019
Adolescent
Adult
Age of Onset
Amino Acid Metabolism, Inborn Errors
Child
Child, Preschool
Cross-Sectional Studies
Disease Progression
Europe
Female
Homocystinuria
Humans
Infant
Infant, Newborn
Male
Methylation
Methylenetetrahydrofolate Reductase (NADPH2)
Methylmalonic Acid
Muscle Spasticity
Phenotype
Pregnancy
Psychotic Disorders
Registries
Retrospective Studies
Vitamin B 12
Young Adult
English
AIM
To explore the clinical presentation, course, treatment and impact of early treatment in patients with remethylation disorders from the European Network and Registry for Homocystinurias and Methylation Defects (E-HOD) international web-based registry.
RESULTS
This review comprises 238 patients (cobalamin C defect n = 161; methylenetetrahydrofolate reductase deficiency n = 50; cobalamin G defect n = 11; cobalamin E defect n = 10; cobalamin D defect n = 5; and cobalamin J defect n = 1) from 47 centres for whom the E-HOD registry includes, as a minimum, data on medical history and enrolment visit. The duration of observation was 127 patient years. In 181 clinically diagnosed patients, the median age at presentation was 30 days (range 1 day to 42 years) and the median age at diagnosis was 3.7 months (range 3 days to 56 years). Seventy-five percent of pre-clinically diagnosed patients with cobalamin C disease became symptomatic within the first 15 days of life. Total homocysteine (tHcy), amino acids and urinary methylmalonic acid (MMA) were the most frequently assessed disease markers; confirmatory diagnostics were mainly molecular genetic studies. Remethylation disorders are multisystem diseases dominated by neurological and eye disease and failure to thrive. In this cohort, mortality, thromboembolic, psychiatric and renal disease were rarer than reported elsewhere. Early treatment correlates with lower overall morbidity but is less effective in preventing eye disease and cognitive impairment. The wide variation in treatment hampers the evaluation of particular therapeutic modalities.
CONCLUSION
Treatment improves the clinical course of remethylation disorders and reduces morbidity, especially if started early, but neurocognitive and eye symptoms are less responsive. Current treatment is highly variable. This study has the inevitable limitations of a retrospective, registry-based design.
To explore the clinical presentation, course, treatment and impact of early treatment in patients with remethylation disorders from the European Network and Registry for Homocystinurias and Methylation Defects (E-HOD) international web-based registry.
RESULTS
This review comprises 238 patients (cobalamin C defect n = 161; methylenetetrahydrofolate reductase deficiency n = 50; cobalamin G defect n = 11; cobalamin E defect n = 10; cobalamin D defect n = 5; and cobalamin J defect n = 1) from 47 centres for whom the E-HOD registry includes, as a minimum, data on medical history and enrolment visit. The duration of observation was 127 patient years. In 181 clinically diagnosed patients, the median age at presentation was 30 days (range 1 day to 42 years) and the median age at diagnosis was 3.7 months (range 3 days to 56 years). Seventy-five percent of pre-clinically diagnosed patients with cobalamin C disease became symptomatic within the first 15 days of life. Total homocysteine (tHcy), amino acids and urinary methylmalonic acid (MMA) were the most frequently assessed disease markers; confirmatory diagnostics were mainly molecular genetic studies. Remethylation disorders are multisystem diseases dominated by neurological and eye disease and failure to thrive. In this cohort, mortality, thromboembolic, psychiatric and renal disease were rarer than reported elsewhere. Early treatment correlates with lower overall morbidity but is less effective in preventing eye disease and cognitive impairment. The wide variation in treatment hampers the evaluation of particular therapeutic modalities.
CONCLUSION
Treatment improves the clinical course of remethylation disorders and reduces morbidity, especially if started early, but neurocognitive and eye symptoms are less responsive. Current treatment is highly variable. This study has the inevitable limitations of a retrospective, registry-based design.
- Language
-
- English
- Open access status
- closed
- Identifiers
-
- DOI 10.1002/jimd.12041
- PMID 30773687
- Persistent URL
- https://folia.unifr.ch/global/documents/285525
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