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The cblD defect causes either isolated or combined deficiency of methylcobalamin and adenosylcobalamin synthesis

Suormala, Terttu and Baumgartner, Matthias R. and Coelho, David and Zavadakova, Petra and Kozich, Viktor and Koch, Hans Georg and Berghaüser, Martin and Wraith, James E. and Burlina, Alberto and Sewell, Adrian and Herwig, Jürgen and Fowler, Brian. (2004) The cblD defect causes either isolated or combined deficiency of methylcobalamin and adenosylcobalamin synthesis. Journal of biological chemistry, Vol. 279, no. 41. pp. 42742-42749.

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Official URL: http://edoc.unibas.ch/dok/A5253387

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Abstract

Intracellular cobalamin is converted to adenosylcobalamin, coenzyme for methylmalonyl-CoA mutase and to methylcobalamin, coenzyme for methionine synthase, in an incompletely understood sequence of reactions. Genetic defects of these steps are defined as cbl complementation groups of which cblC, cblD (described in only two siblings), and cblF are associated with combined homocystinuria and methylmalonic aciduria. Here we describe three unrelated patients belonging to the cblD complementation group but with distinct biochemical phenotypes different from that described in the original cblD siblings. Two patients presented with isolated homocystinuria and reduced formation of methionine and methylcobalamin in cultured fibroblasts, defined as cblD-variant 1, and one patient with isolated methylmalonic aciduria and deficient adenosylcobalamin synthesis in fibroblasts, defined as cblD-variant 2. Cell lines from the cblD-variant 1 patients clearly complemented reference lines with the same biochemical phenotype, i.e. cblE and cblG, and the cblD-variant 2 cell line complemented cells from the mutant classes with isolated deficiency of adenosylcobalamin synthesis, i.e. cblA and cblB. Also, no pathogenic sequence changes in the coding regions of genes associated with the respective biochemical phenotypes were found. These findings indicate heterogeneity within the previously defined cblD mutant class and point to further complexity of intracellular cobalamin metabolism.
Faculties and Departments:03 Faculty of Medicine > Bereich Kinder- und Jugendheilkunde (Klinik) > Ehemalige Einheiten Pädiatrie (UKBB) > Labor (Fowler)
03 Faculty of Medicine > Departement Klinische Forschung > Bereich Kinder- und Jugendheilkunde (Klinik) > Ehemalige Einheiten Pädiatrie (UKBB) > Labor (Fowler)
UniBasel Contributors:Fowler, Brian
Item Type:Article, refereed
Article Subtype:Book Review
Bibsysno:Link to catalogue
Publisher:American Society of Biological Chemists
ISSN:0021-9258
Note:Publication type according to Uni Basel Research Database: Journal item
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Last Modified:22 Mar 2012 14:23
Deposited On:22 Mar 2012 13:34

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