Abstract
Background
Methylmalonic aciduria with homocystinuria, cblC defect, is the most frequent disorder of vitamin B12 metabolism. CblC patients are commonly treated with a multidrug therapy to reduce metabolite accumulation and to increase deficient substrates. However the long-term outcome is often unsatisfactory especially in patients with early onset, with frequent progression of neurological and ocular impairment. Recent studies, have shown perturbation of cellular redox status in cblC. To evaluate the potential contribution of oxidative stress into the patophysiology of cblC defect, we have analyzed the in vivo glutathione metabolism in a large series of cblC deficient individuals.
Methods
Levels of different forms of glutathione were measured in lymphocytes obtained from 18 cblC patients and compared with age-matched controls. Furthermore, we also analyzed plasma cysteine and total homocysteine.
Results
We found an imbalance of glutathione metabolism in cblC patients with a significant decrease of total and reduced glutathione, along with a significant increase of different oxidized glutathione forms.
Conclusions
These findings show a relevant in vivo disturbance of glutathione metabolism underlining the contribution of glutathione pool depletion to the redox imbalance in treated cblC patients. Our study may be helpful in addressing future research to better understanding the pathogenetic mechanism of the disease and in developing new therapeutic approaches, including the use of novel vitamin B12 derivatives.
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Acknowledgment
The financial support of Mariani Foundation of Milan (Grant n. R-12-92) is gratefully acknowledged.
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The study was financed by Mariani Foundation of Milan (Grant n. R-12-92). The authors confirm independence from the sponsors; the content of the article has not been influenced by sponsors.
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Communicated by: Brian Fowler
Anna Pastore and Diego Martinelli these authors contributed equally to this work.
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Pastore, A., Martinelli, D., Piemonte, F. et al. Glutathione metabolism in cobalamin deficiency type C (cblC). J Inherit Metab Dis 37, 125–129 (2014). https://doi.org/10.1007/s10545-013-9605-3
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DOI: https://doi.org/10.1007/s10545-013-9605-3