Update on transcobalamin deficiency: Clinical presentation, treatment and outcome

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. VaretC. P. Venditti, D. Zafeiriou, C. A. Rupar, D. S. Rosenblatt, D. Watkins, N. Braverman

Research output: Contribution to journalArticle

24 Citations (Scopus)

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 bymolecular 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.

Original languageEnglish
Pages (from-to)461-473
Number of pages13
JournalJournal of Inherited Metabolic Disease
Volume37
Issue number3
DOIs
StatePublished - Jan 1 2014

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Transcobalamins
Vitamin B 12
Methylmalonic Acid
Homocysteine
Urine
Megaloblastic Anemia
Pallor
Therapeutics
Severe Combined Immunodeficiency
Agammaglobulinemia
Failure to Thrive
Pancytopenia
Intramuscular Injections
Anemia
Diarrhea
Blood Cells
Leukemia
Fibroblasts
Injections

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics

Cite this

Trakadis, Y. J., Alfares, A., Bodamer, O. A., Buyukavci, M., Christodoulou, J., Connor, P., ... Braverman, N. (2014). Update on transcobalamin deficiency: Clinical presentation, treatment and outcome. Journal of Inherited Metabolic Disease, 37(3), 461-473. https://doi.org/10.1007/s10545-013-9664-5

Update on transcobalamin deficiency : Clinical presentation, treatment and outcome. / Trakadis, Y. J.; Alfares, A.; Bodamer, O. A.; Buyukavci, M.; Christodoulou, J.; Connor, P.; Glamuzina, E.; Gonzalez-Fernandez, F.; Bibi, H.; Echenne, B.; Manoli, I.; Mitchell, J.; Nordwall, M.; Prasad, C.; Scaglia, F.; Schiff, M.; Schrewe, B.; Touati, G.; Tchan, M. C.; Varet, B.; Venditti, C. P.; Zafeiriou, D.; Rupar, C. A.; Rosenblatt, D. S.; Watkins, D.; Braverman, N.

In: Journal of Inherited Metabolic Disease, Vol. 37, No. 3, 01.01.2014, p. 461-473.

Research output: Contribution to journalArticle

Trakadis, YJ, Alfares, A, Bodamer, OA, Buyukavci, M, Christodoulou, J, Connor, P, Glamuzina, E, Gonzalez-Fernandez, F, Bibi, H, Echenne, B, Manoli, I, Mitchell, J, Nordwall, M, Prasad, C, Scaglia, F, Schiff, M, Schrewe, B, Touati, G, Tchan, MC, Varet, B, Venditti, CP, Zafeiriou, D, Rupar, CA, Rosenblatt, DS, Watkins, D & Braverman, N 2014, 'Update on transcobalamin deficiency: Clinical presentation, treatment and outcome', Journal of Inherited Metabolic Disease, vol. 37, no. 3, pp. 461-473. https://doi.org/10.1007/s10545-013-9664-5
Trakadis YJ, Alfares A, Bodamer OA, Buyukavci M, Christodoulou J, Connor P et al. Update on transcobalamin deficiency: Clinical presentation, treatment and outcome. Journal of Inherited Metabolic Disease. 2014 Jan 1;37(3):461-473. https://doi.org/10.1007/s10545-013-9664-5
Trakadis, Y. J. ; Alfares, A. ; Bodamer, O. A. ; Buyukavci, M. ; Christodoulou, J. ; Connor, P. ; Glamuzina, E. ; Gonzalez-Fernandez, F. ; Bibi, H. ; Echenne, B. ; Manoli, I. ; Mitchell, J. ; Nordwall, M. ; Prasad, C. ; Scaglia, F. ; Schiff, M. ; Schrewe, B. ; Touati, G. ; Tchan, M. C. ; Varet, B. ; Venditti, C. P. ; Zafeiriou, D. ; Rupar, C. A. ; Rosenblatt, D. S. ; Watkins, D. ; Braverman, N. / Update on transcobalamin deficiency : Clinical presentation, treatment and outcome. In: Journal of Inherited Metabolic Disease. 2014 ; Vol. 37, No. 3. pp. 461-473.
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