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Methylmalonic acidaemia: Examination of genotype and biochemical data in 32 patients belonging to mut, cblA or cblB complementation group

Lookup NU author(s): Dr Morteza Pourfarzam


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Methylmalonic acidaemia (MMA) is a genetic disorder caused by defects in methylmalonyl-CoA mutase or in any of the different proteins involved in the synthesis of adenosylcobalamin. The aim of this work was to examine the biochemical and clinical phenotype of 32 MMA patients according to their genotype, and to study the mutant mRNA stability by real-time PCR analysis. Using cellular and biochemical methods, we classified our patient cohort as having the MMA forms mut (n=19), cblA (n=9) and cblB (n=4). All the mut0 and some of the cblB patients had the most severe clinical and biochemical manifestations, displaying non-inducible propionate incorporation in the presence of hydroxocobalamin (OHCbl) in vitro and high plasma odd-numbered long-chain fatty acid (OLCFA) concentrations under dietary therapy. In contrast, mut- and cblA patients exhibited a milder phenotype with propionate incorporation enhanced by OHCbl and normal OLCFA levels under dietary therapy. No missense mutations identified in the MUT gene, including mut0 and mut- changes, affected mRNA stability. A new sequence variation (c.562G>C) in the MMAA gene was identified. Most of the cblA patients carried premature termination codons (PTC) in both alleles. Interestingly, the transcripts containing the PTC mutations were insensitive to nonsense-mediated decay (NMD). © Springer Science+Business Media B.V. 2008.

Publication metadata

Author(s): Merinero B, Perez B, Perez-Cerda C, Rincon A, Desviat LR, Martinez MA, Sala RP, Garcia MJ, Aldamiz-Echevarria L, Campos J, Cornejo V, del Toro M, Mahfoud A, Martinez-Pardo M, Parini R, Pedron C, Pena-Quintana L, Perez M, Pourfarzam M, Ugarte M

Publication type: Article

Publication status: Published

Journal: Journal of Inherited Metabolic Disease

Year: 2008

Volume: 31

Issue: 1

Pages: 55-66

Print publication date: 01/02/2008

ISSN (print): 0141-8955

ISSN (electronic): 1573-2665

Publisher: Springer Netherlands


DOI: 10.1007/s10545-007-0667-y

PubMed id: 17957493


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