Metabolic cooperation among cell lines from patients with inborn errors of vitamin B12 metabolism: differential response of cblC and cblD.

Human skin fibroblasts derived from patients with all seven known inborn errors of vitamin B12 metabolism have been studied for functional integrity of methylmalonyl CoA mutase and methionine synthase. Cocultivation of cblC and cblF fibroblasts in the absence of polyethylene glycol resulted in a twofold increase over the expected in both [14C]propionate and [14C]methyltetrahydrofolate incorporation into acid-precipitable material, suggesting that metabolic cooperation between cells occurs. This correction in phenotype seems to be mutant class selective since cblD fibroblasts, which are biochemically similar to cblC cells, do not cooperate metabolically when mixed with cblF cells. These observations lend further support to the division of cblC and cblD diseases into discrete classes.