Abstract
Currently, six inborn errors of metabolism with 3-methylglutaconic aciduria as discriminative feature are known. The “Primary 3-methylglutaconic aciduria,” 3-methylglutaconyl-CoA hydratase deficiency or AUH defect, is a disorder of leucine catabolism. For all other subtypes, also denoted “Secondary 3-methylglutaconic acidurias” (TAZ defect or Barth syndrome, SERAC1 defect or MEGDEL syndrome, OPA3 defect or Costeff syndrome, DNAJC19 defect or DCMA syndrome, TMEM70 defect, “not otherwise specified (NOS) 3-MGA-uria”), the origin of 3-methylglutaconic aciduria remains enigmatic but is hypothesized to be independent from leucine catabolism. Here we show the results of leucine loading test in 21 patients with different inborn errors of metabolism who present with 3-methylglutaconic aciduria. After leucine loading urinary 3-methylglutaconic acid levels increased only in the patients with an AUH defect. This strongly supports the hypothesis that 3-methylglutaconic aciduria is independent from leucine breakdown in other inborn errors of metabolism with 3-methylglutaconic aciduria and also provides a simple test to discriminate between primary and secondary 3-methylglutaconic aciduria in regular patient care.
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Communicated by: Jerry Vockley, M.D., Ph.D.
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Saskia B. Wortmann, Leo A.J. Kluijtmans, Silvia Sequeira, Ron A. Wevers, and Eva Morava declare that they have no conflict of interest.
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All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2000 (5). Oral informed consent was obtained from all patients for being included in the study.
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Saskia B. Wortmann and Eva Morava planned the study. Saskia B. Wortmann, Silvia Sequeira, and Eva Morava conducted the study in patients. Leo A.J. Kluijtmans and Ron A. Wevers conducted the biochemical measurements. All authors interpreted and discussed the results. Saskia B. Wortmann wrote the manuscript which was read and corrected by all authors.
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Wortmann, S.B., Kluijtmans, L.A.J., Sequeira, S., Wevers, R.A., Morava, E. (2014). Leucine Loading Test is Only Discriminative for 3-Methylglutaconic Aciduria Due to AUH Defect. In: Zschocke, J., Gibson, K., Brown, G., Morava, E., Peters, V. (eds) JIMD Reports Volume 16. JIMD Reports, vol 16. Springer, Berlin, Heidelberg. https://doi.org/10.1007/8904_2014_309
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DOI: https://doi.org/10.1007/8904_2014_309
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