Abstract
Classical neonatal-onset glutaric aciduria type 2 (MAD deficiency) is a severe disorder of mitochondrial fatty acid oxidation associated with poor survival. Secondary dysfunction of acyl-CoA dehydrogenases may result from deficiency for riboflavin transporters, leading to severe disorders that, nevertheless, are treatable by riboflavin supplementation. In the last 10 years, we identified nine newborns with biochemical features consistent with MAD deficiency, only four of whom survived past the neonatal period. A likely iatrogenic cause of riboflavin deficiency was found in two premature newborns having parenteral nutrition, one of whom recovered upon multivitamin supplementation, whereas the other died before diagnosis. Four other patients had demonstrated mutations involving ETF or ETF-DH flavoproteins, whereas the remaining three patients presumably had secondary deficiencies of unknown mechanism. Interestingly, six newborns among the seven tested for plasma amino acids had pronounced hyperprolinemia. In one case, because the initial diagnostic workup did not include organic acids and acylcarnitine profiling, clinical presentation and hyperprolinemia suggested the diagnosis. Analysis of our full cohort of >50,000 samples from >30,000 patients suggests that the proline/alanine ratio may be a good marker of MAD deficiency and could contribute to a more effective management of the treatable forms.
Competing interests: None declared
C. Pontoizeau and F. Habarou equally contributed to this book.
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Acknowledgments
We thank Jacqueline Bardet, Odile Beaugendre, Marie Bisançon, Martine Gasquet, and Sabine Leroy for excellent technical assistance.
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Communicated by: Michael J Bennett, PhD
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Synopsis
Hyperprolinemia and more precisely high proline/alanine ratio may be a good marker of MAD deficiency.
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Clément Pontoizeau, Florence Habarou, Anaïs Brassier, Alice Veauville-Merllié, Coraline Grisel, Jean-Baptiste Arnoux, Christine Vianey-Saban, Robert Barouki, Bernadette Chadefaux-Vekemans, Cécile Acquaviva, Pascale de Lonlay, and Chris Ottolenghi 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. Informed consent was obtained from all patients for being included in the study.
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AB, CG, J-BA, and PdL collected the data. CP, FH, AVM, CVS, CA, PdL, and CO analyzed the data. CP, FH, CVS, CA, PdL, and CO wrote the manuscript. All authors read and approved the final manuscript.
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Pontoizeau, C. et al. (2015). Hyperprolinemia in Type 2 Glutaric Aciduria and MADD-Like Profiles. In: Morava, E., Baumgartner, M., Patterson, M., Rahman, S., Zschocke, J., Peters, V. (eds) JIMD Reports, Volume 27. JIMD Reports, vol 27. Springer, Berlin, Heidelberg. https://doi.org/10.1007/8904_2015_481
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DOI: https://doi.org/10.1007/8904_2015_481
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