Abstract
Coenzyme Q10 deficiency is a clinically and genetically heterogeneous disorder, with manifestations that may range from fatal neonatal multisystem failure, to adult-onset encephalopathy. We report a patient who presented at birth with severe lactic acidosis, proteinuria, dicarboxylic aciduria, and hepatic insufficiency. She also had dilation of left ventricle on echocardiography. Her neurological condition rapidly worsened and despite aggressive care she died at 23 h of life. Muscle histology displayed lipid accumulation. Electron microscopy showed markedly swollen mitochondria with fragmented cristae. Respiratory-chain enzymatic assays showed a reduction of combined activities of complex I+III and II+III with normal activities of isolated complexes. The defect was confirmed in fibroblasts, where it could be rescued by supplementing the culture medium with 10 μ M coenzyme Q10. Coenzyme Q10 levels were reduced (28% of controls) in these cells. We performed exome sequencing and focused the analysis on genes involved in coenzyme Q10 biosynthesis. The patient harbored a homozygous c.545T>G, p.(Met182Arg) alteration in COQ2, which was validated by functional complementation in yeast. In this case the biochemical and morphological features were essential to direct the genetic diagnosis. The parents had another pregnancy after the biochemical diagnosis was established, but before the identification of the genetic defect. Because of the potentially high recurrence risk, and given the importance of early CoQ10 supplementation, we decided to treat with CoQ10 the newborn child pending the results of the biochemical assays. Clinicians should consider a similar management in siblings of patients with CoQ10 deficiency without a genetic diagnosis.
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Acknowledgements
This work was supported by grants from Fondazione CARIPARO, Telethon Italy GGP13222 and University of Padova (CPDA123573/12) to LS; Telethon Italy GGP10121 and PRIN 20108WT59Y_003 to OZ; Italian Ministry of Health (GR-2009-1578914) to ET; Spanish FIS grant PI11-00078 and Proyecto Excelencia P08-CTS-03988 to PN.
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Desbats, M., Vetro, A., Limongelli, I. et al. Primary coenzyme Q10 deficiency presenting as fatal neonatal multiorgan failure. Eur J Hum Genet 23, 1254–1258 (2015). https://doi.org/10.1038/ejhg.2014.277
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DOI: https://doi.org/10.1038/ejhg.2014.277
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