METHYLMALONIC ACIDURIAS - mut0/mut- and cblC Defects in Portuguese Population

Célia Nogueira, Marta Marques, Laura Vilarinho

Abstract

The methylmalonic acidurias (MMAs) are metabolic disorders resulting from deficient methylmalonyl-CoA mutase (MCM) activity, a vitamin B12-dependent enzyme that uses adenosylcobalamin (Ado-Cbl) as a cofactor. Several mutant genetic classes that cause MMA are known based on biochemical, enzymatic and genetic complementation analysis. The mut0/mut- defects result from deficiency of MCM, while the cblA, cblB and the variant 2 form of cblD complementation groups are linked to processes unique to Ado-Cbl synthesis. The cblC, cblD and cblF complementation groups are associated with defective methyl-cobalamin synthesis as well. Mutations in the genes associated with most of these defects have been described. In this study we investigate at molecular level four patients with mut0/mut- MMA phenotype and 19 Portuguese patients with cblC defect. We found four different mutations already described in the literature, in each MUT and MMACHC genes, respectively. Our data showed an evident difference in the prevalence of these two diseases, compared with other countries worldwide.

References

  1. Acquaviva C., Elion J., 2005. Molecular basis of methylmalonyl-CoA mutase apoenzyme defect in 40 European patients affected by mut(o) and mut- forms of methylmalonic acidemia: identification of 29 novel mutations in the MUT gene. Hum Mutat., 25(2):167- 76.
  2. Fenton W., Rosenblatt D., 2001. Disorders of propionate and methylmalonate metabolism. In: Scriver CR, Beaudet AL, Sly WS, Valle D, editors. The metabolic and molecular basis of inherited disease. New York: McGraw-Hill. P 2165-2193.
  3. Fuchshuber A, Hildebrandt F., 2000. Mut0 methylmalonic acidemia: eleven novel mutations of the methylmalonyl CoA mutase including a deletioninsertion mutation. Hum Mutat., 16(2):179.
  4. Jansen R., Ledley F., 1989. Cloning of full-length methylmalonyl-CoA mutase from a cDNA library using the polymerase chain reaction. Genomics, 4:198-205.
  5. Lerner-Ellis J.P., Rosenblatt D.S., 2006. Identification of the generesponsible for methylmalonic aciduria and homocystinuria, cblC type. Nat. Genet., 38 93-100.
  6. Nogueira C., Dionisi-Vici C., 2008. Spectrum of MMACHC mutations in Italian and Portuguese patients with combined methylmalonic aciduria and homocystinuria, cblC type. Mol Genet Metab. 93(4):475-80.
  7. Richard E., Pérez B., 2009. Genetic and cellular studies of oxidative stress in methylmalonic aciduria (MMA) cobalamin deficiency type C (cblC) with homocystinuria (MMACHC). Hum Mutat., 16 [Epub ahead of print].
  8. Rosenblatt D., Seashore M., 1997. Clinical heterogeneity and prognosis in combined methylmalonic aciduria and homocystinuria (cblC). J. Inherit. Metab. Dis., 20 528-538.
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Paper Citation


in Harvard Style

Nogueira C., Marques M. and Vilarinho L. (2010). METHYLMALONIC ACIDURIAS - mut0/mut- and cblC Defects in Portuguese Population . In Proceedings of the First International Conference on Bioinformatics - Volume 1: BIOINFORMATICS, (BIOSTEC 2010) ISBN 978-989-674-019-1, pages 261-263. DOI: 10.5220/0002759802610263


in Bibtex Style

@conference{bioinformatics10,
author={Célia Nogueira and Marta Marques and Laura Vilarinho},
title={METHYLMALONIC ACIDURIAS - mut0/mut- and cblC Defects in Portuguese Population},
booktitle={Proceedings of the First International Conference on Bioinformatics - Volume 1: BIOINFORMATICS, (BIOSTEC 2010)},
year={2010},
pages={261-263},
publisher={SciTePress},
organization={INSTICC},
doi={10.5220/0002759802610263},
isbn={978-989-674-019-1},
}


in EndNote Style

TY - CONF
JO - Proceedings of the First International Conference on Bioinformatics - Volume 1: BIOINFORMATICS, (BIOSTEC 2010)
TI - METHYLMALONIC ACIDURIAS - mut0/mut- and cblC Defects in Portuguese Population
SN - 978-989-674-019-1
AU - Nogueira C.
AU - Marques M.
AU - Vilarinho L.
PY - 2010
SP - 261
EP - 263
DO - 10.5220/0002759802610263