3-Methylglutaconic aciduria-lessons from 50 genes and 977 patients

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dc.contributor.author Wortmann, Saskia B.
dc.contributor.author Kluijtmans, Leo A. J.
dc.contributor.author Rodenburg, Richard J.
dc.contributor.author Sass, Jörn Oliver
dc.contributor.author Nouws, Jessica
dc.contributor.author Van Kaauwen, Edwin P.
dc.contributor.author Kleefstra, Tjitske
dc.contributor.author Tranebjaerg, Lisbeth
dc.contributor.author De Vries, Maaike C.
dc.contributor.author Isohanni, Pirjo
dc.contributor.author Walter, Katharina
dc.contributor.author Alkuraya, Fowzan S.
dc.contributor.author Smuts, Izelle
dc.contributor.author Reinecke, Carolus J.
dc.contributor.author an der Westhuizen, Francois Hendrikus
dc.contributor.author Thorburn, David
dc.contributor.author Smeitink, Jan A.M.
dc.contributor.author Morava, Eva
dc.contributor.author Wevers, Ron A.
dc.date.accessioned 2014-10-23T08:18:46Z
dc.date.available 2014-10-23T08:18:46Z
dc.date.issued 2013-11
dc.description.abstract Elevated urinary excretion of 3-methylglutaconic acid is considered rare in patients suspected of a metabolic disorder. In 3-methylglutaconyl-CoA hydratase deficiency (mutations in AUH), it derives from leucine degradation. In all other disorders with 3-methylglutaconic aciduria the origin is unknown, yet mitochondrial dysfunction is thought to be the common denominator. We investigate the biochemical, clinical and genetic data of 388 patients referred to our centre under suspicion of a metabolic disorder showing 3-methylglutaconic aciduria in routine metabolic screening. Furthermore, we investigate 591 patients with 50 different, genetically proven, mitochondrial disorders for the presence of 3-methylglutaconic aciduria. Three percent of all urine samples of the patients referred showed 3- methylglutaconic aciduria, often in correlation with disorders not reported earlier in association with 3-methylglutaconic aciduria (e.g. organic acidurias, urea cycle disorders, haematological and neuromuscular disorders). In the patient cohort with genetically proven mitochondrial disorders 11 % presented 3-methylglutaconic aciduria. It was more frequently seen in ATPase related disorders, with mitochondrial DNA depletion or deletion, but not in patients with single respiratory chain complex deficiencies. Besides, it was a consistent feature of patients with mutations in TAZ, SERAC1, OPA3, DNAJC19 and TMEM70 accounting for mitochondrial membrane related pathology. 3-methylglutaconic aciduria is found quite frequently in patients suspected of a metabolic disorder, and mitochondrial dysfunction is indeed a common denominator. It is only a discriminative feature of patients with mutations in AUH, TAZ, SERAC1, OPA3, DNAJC19 TMEM70. These conditions should therefore be referred to as inborn errors of metabolism with 3-methylglutaconic aciduria as discriminative feature. en_US
dc.description.librarian hb2014 en_US
dc.description.uri http://link.springer.com/journal/10545 en_US
dc.identifier.citation Wortmann, SB, Kluijtmans, LAJ, Rodenburg, RJ, Sass, JO, Nouws, J, Van Kaauwen, EP, Kleefstra, T, Tranebjaerg, L, De Vries, MC, Isohanni, P, Walter, K, Alkuraya, F, Smuts, I, Reinecke, C, Van der Westhuizen, H, Thorburn, D, Smeitink, JAM, Morava, E & Wevers, RA 2013, '3-Methylglutaconic aciduria-lessons from 50 genes and 977 patients', Journal of Inherited Metabolic Disease, vol. 36, no. 6, pp. 913-921. en_US
dc.identifier.issn 0141-8955 (print)
dc.identifier.issn 1573-2665 (online)
dc.identifier.other 10.1007/s10545-012-9579-6
dc.identifier.uri http://hdl.handle.net/2263/42438
dc.language.iso en en_US
dc.publisher Springer en_US
dc.rights © SSIEM and Springer Science+Business Media Dordrecht 2013. The original publication is available at : http://link.springer.com/journal/10545. en_US
dc.subject 3-Methylglutaconic aciduria en_US
dc.subject Patients en_US
dc.subject Metabolic disorder en_US
dc.title 3-Methylglutaconic aciduria-lessons from 50 genes and 977 patients en_US
dc.type Postprint Article en_US


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