Primary coenzyme Q 10 deficiency presenting as fatal neonatal multiorgan failure

Maria Andrea Desbats, Annalisa Vetro, Ivan Limongelli, Giada Lunardi, Alberto Casarin, Mara Doimo, Marco Spinazzi, Corrado Angelini, Giovanna Cenacchi, Alberto Burlina, Maria Angeles Rodriguez Hernandez, Lino Chiandetti, Maurizio Clementi, Eva Trevisson, Placido Navas, Orsetta Zuffardi, Leonardo Salviati

Research output: Contribution to journalArticle

Abstract

Coenzyme Q 10 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 μM coenzyme Q 10. Coenzyme Q 10 levels were reduced (28% of controls) in these cells. We performed exome sequencing and focused the analysis on genes involved in coenzyme Q 10 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 CoQ 10 supplementation, we decided to treat with CoQ 10 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.

Original languageEnglish
Pages (from-to)1254-1258
Number of pages5
JournalEuropean Journal of Human Genetics
Volume23
Issue number9
DOIs
Publication statusPublished - Sep 14 2015

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics

Fingerprint Dive into the research topics of 'Primary coenzyme Q 10 deficiency presenting as fatal neonatal multiorgan failure'. Together they form a unique fingerprint.

Cite this