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Should transcobalamin deficiency be treated aggressively?
- Source :
-
Journal of inherited metabolic disease [J Inherit Metab Dis] 2010 Jun; Vol. 33 (3), pp. 223-9. Date of Electronic Publication: 2010 Mar 30. - Publication Year :
- 2010
-
Abstract
- Transcobalamin (transcobalamin II, TC) transports plasma vitamin B(12) (cobalamin, Cbl) into cells. TC deficiency is a rare autosomal recessive disorder causing intracellular Cbl depletion, which in turn causes megaloblastic bone marrow failure, accumulation of homocysteine and methylmalonic acid, and methionine depletion. The clinical presentation reflects intracellular Cbl defects, with early-onset failure to thrive with gastrointestinal symptoms, pancytopenia, and megaloblastic anemia, sometimes followed by neurological complications. We report the clinical, biological, and molecular findings and the outcome in five TC-deficient patients. The three treated early had an initial favorable outcome, whereas the two treated inadequately had late-onset severe neuro-ophthalmological impairment. Even if the natural course of the disease over time might also result in late-onset symptoms in the aggressively treated patients, these data emphasize that TC deficiency is a severe disorder requiring early detection and probably long-term aggressive therapy. Mutation analysis revealed six unreported mutations in the TCN2 gene. In silico structural analysis showed that these mutations disrupt the Cbl-TC interaction domain and/or the putative transcobalamin-transcobalamin receptor interaction domain.
- Subjects :
- Anemia, Megaloblastic therapy
Biological Transport
DNA Mutational Analysis
DNA Primers genetics
Female
Homocysteine chemistry
Humans
Infant
Infant, Newborn
Methionine metabolism
Methylmalonic Acid metabolism
Mutation
Polymerase Chain Reaction
Protein Structure, Tertiary
Transcobalamins deficiency
Transcobalamins metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1573-2665
- Volume :
- 33
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Journal of inherited metabolic disease
- Publication Type :
- Academic Journal
- Accession number :
- 20352340
- Full Text :
- https://doi.org/10.1007/s10545-010-9074-x