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Update on transcobalamin deficiency: clinical presentation,treatment and outcome |
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| Authors: | Y. J. Trakadis A. Alfares O. A. Bodamer M. Buyukavci J. Christodoulou P. Connor E. Glamuzina F. Gonzalez-Fernandez H. Bibi B. Echenne I. Manoli J. Mitchell M. Nordwall C. Prasad F. Scaglia M. Schiff B. Schrewe G. Touati M. C. Tchan B. Varet C. P. Venditti D. Zafeiriou C. A. Rupar D. S. Rosenblatt D. Watkins N. Braverman |
| Affiliation: | 1. Department of Medical Genetics, McGill University Health Centre, Montreal, QC, Canada 20. Montreal Children’s Hospital, McGill University Health Centre, Montreal, QC, Canada 2. Departments of Human Genetics, Biochemistry and Molecular Biology, University of Miami, Miami, FL, USA 3. Faculty of Medicine Division of Pediatric Hematology/Oncology Erzurum, Atatürk University, Erzurum, Turkey 4. Western Sydney Genetics Program, Children’s Hospital at Westmead and Disciplines of Genetic Medicine & Paediatrics and Child Health, University of Sydney, Sydney, Australia 5. Department of Haematology, Children’s Hospital for Wales Heath Park, Cardiff, UK 6. Adult and Paediatric National Metabolic Service, Starship Children’s Hospital, Auckland, New Zealand 7. Servicio de Hematología y Hemoterapia, Sección de Eritropatología, Hospital Clínico San Carlos de Madrid, Madrid, Spain 8. Pediatric Department Barzilai Medical Center, Ashkelon, Affiliated with the Ben Gurion University of the Negev, Beer Sheva, Israel 9. Service de Neuropédiatrie, H?pital gui de Chauliac, 34295, Montpellier, France 10. Genetics and Molecular Biology Branch, National Human Genome Research Institute, NIH, Bethesda, MD, USA 11. Division of Paediatrics, Vrinnevi Hospital, Norrk?ping, County of ?sterg?tland, Sweden 12. Departments of Pediatrics, London Health Sciences Centre and Western University London, London, ON, Canada 13. Departments of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA 14. Reference Center for Metabolic Disease, Robert Debré University Hospital, Paris, France 15. Centre for Inherited Metabolic Disorders, Necker-Enfants Malades Hospital AP-HP, Universit_Paris Descartes, Paris, France 16. Department of Genetic Medicine, Westmead Hospital, Sydney, Australia and Discipline of Genetic Medicine, Sydney Medical School, University of Sydney, Sydney, Australia 17. Department of Hematology, Paris Descartes University, Necker Hospital, Paris, France 18. Department of Paediatrics, Aristotle University of Thessaloniki, Hippokration General Hospital, Thessaloniki, Greece 19. Departments of Biochemistry, Pediatrics and the Children’s Health Research Institute, Western University, London, ON, Canada |
| Abstract: | Transcobalamin (TC) transports cobalamin from blood into cells. TC deficiency is a rare autosomal recessive disorder usually presenting in early infancy with failure to thrive, weakness, diarrhoea, pallor, anemia, and pancytopenia or agammaglobulinemia. It can sometimes resemble neonatal leukemia or severe combined immunodeficiency disease. Diagnosis of TC deficiency is suspected based on megaloblastic anemia, elevation of total plasma homocysteine, and blood or urine methylmalonic acid. It is confirmed by studying the synthesis of TC in cultured fibroblasts, or by molecular analysis of the TCN2 gene. TC deficiency is treatable with supplemental cobalamin, but the optimal type, route and frequency of cobalamin administration and long term patient outcomes are unknown. Here we present a series of 30 patients with TC deficiency, including an update on multiple previously published patients, in order to evaluate the different treatment strategies and provide information about long term outcome. Based on the data presented, current practice appears to favour treatment of individuals with TC deficiency by intramuscular injections of hydroxy- or cyanocobalamin. In most cases presented, at least weekly injections (1 mg IM) were necessary to ensure optimal treatment. Most centres adjusted the treatment regimen based on monitoring CBC, total plasma homocysteine, plasma and urine methylmalonic acid, as well as, clinical status. Finally, continuing IM treatment into adulthood appears to be beneficial. |
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