title: Primary coenzyme Q10 deficiency presenting as fatal neonatal multiorgan failure.
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 μM 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.
authors.affiliation: 1] Clinical Genetics Unit, Department of Woman and Child Health, University of Padova, Padova, Italy [2] IRP Città della Speranza, Padova, Italy.
authors.forename: Maria Andrea
authors.initials: MA
authors.lastname: Desbats
authors.affiliation: Biotechnology Research Laboratory, Foundation IRCCS, Policlinico San Matteo, Pavia, Italy.
authors.forename: Annalisa
authors.initials: A
authors.lastname: Vetro
authors.affiliation: 1] Department of Industrial and Information Engineering, University of Pavia, Pavia, Italy [2] Department of Molecular Medicine, University of Pavia, Pavia, Italy.
authors.forename: Ivan
authors.identifier: 0000000297812974
authors.initials: I
authors.lastname: Limongelli
authors.affiliation: 1] Clinical Genetics Unit, Department of Woman and Child Health, University of Padova, Padova, Italy [2] IRP Città della Speranza, Padova, Italy.
authors.forename: Giada
authors.initials: G
authors.lastname: Lunardi
authors.affiliation: 1] Clinical Genetics Unit, Department of Woman and Child Health, University of Padova, Padova, Italy [2] IRP Città della Speranza, Padova, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Casarin
authors.affiliation: 1] Clinical Genetics Unit, Department of Woman and Child Health, University of Padova, Padova, Italy [2] IRP Città della Speranza, Padova, Italy.
authors.forename: Mara
authors.initials: M
authors.lastname: Doimo
authors.affiliation: Neuromuscular Laboratory, Department of Neurosciences, University of Padova, Padova, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Spinazzi
authors.affiliation: 1] Neuromuscular Laboratory, Department of Neurosciences, University of Padova, Padova, Italy [2] Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) San Camillo, Venice, Italy.
authors.forename: Corrado
authors.initials: C
authors.lastname: Angelini
authors.affiliation: Department of Radiological and Histocytopathological Sciences, University of Bologna, Bologna, Italy.
authors.forename: Giovanna
authors.initials: G
authors.lastname: Cenacchi
authors.affiliation: Metabolic Disorders Unit, Azienda Ospedaliera di Padova, Padova, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Burlina
authors.affiliation: Centro Andaluz de Biología del Desarrollo (CABD-CSIC), Universidad Pablo Olavide, and CIBERER, Instituto de Salud Carlos III, Carretera de Utrera Km. 1, Sevilla, Spain.
authors.forename: Maria Angeles
authors.initials: MA
authors.lastname: Rodriguez Hernandez
authors.affiliation: Neonatal Intensive Care Unit, Department of Woman and Child Health, University of Padova, Italy.
authors.forename: Lino
authors.initials: L
authors.lastname: Chiandetti
authors.affiliation: 1] Clinical Genetics Unit, Department of Woman and Child Health, University of Padova, Padova, Italy [2] IRP Città della Speranza, Padova, Italy.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Clementi
authors.affiliation: 1] Clinical Genetics Unit, Department of Woman and Child Health, University of Padova, Padova, Italy [2] IRP Città della Speranza, Padova, Italy.
authors.forename: Eva
authors.initials: E
authors.lastname: Trevisson
authors.affiliation: Centro Andaluz de Biología del Desarrollo (CABD-CSIC), Universidad Pablo Olavide, and CIBERER, Instituto de Salud Carlos III, Carretera de Utrera Km. 1, Sevilla, Spain.
authors.forename: Placido
authors.initials: P
authors.lastname: Navas
authors.affiliation: 1] Department of Molecular Medicine, University of Pavia, Pavia, Italy [2] Mondino National Institute of Neurology Foundation, IRCCS, Pavia, Italy.
authors.forename: Orsetta
authors.initials: O
authors.lastname: Zuffardi
authors.affiliation: 1] Clinical Genetics Unit, Department of Woman and Child Health, University of Padova, Padova, Italy [2] IRP Città della Speranza, Padova, Italy.
authors.forename: Leonardo
authors.initials: L
authors.lastname: Salviati
mesh_terms: D000140:Acidosis, Lactic / Q000097:blood / Q000235:genetics / Q000473:pathology; D019883:Alkyl and Aryl Transferases / Q000172:deficiency / Q000235:genetics*; D001259:Ataxia / Q000097:blood / Q000175:diagnosis* / Q000235:genetics* / Q000473:pathology; D003241:Consanguinity; D017809:Fatal Outcome; D005260:Female; D015870:Gene Expression; D048550:Hepatic Insufficiency / Q000097:blood / Q000235:genetics / Q000473:pathology; D006801:Humans; D007231:Infant, Newborn; D008607:Intellectual Disability / Q000097:blood / Q000235:genetics / Q000473:pathology; D008931:Mitochondria, Muscle / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D028361:Mitochondrial Diseases / Q000097:blood / Q000175:diagnosis* / Q000235:genetics* / Q000473:pathology; D018908:Muscle Weakness / Q000097:blood / Q000175:diagnosis* / Q000235:genetics* / Q000473:pathology; D018482:Muscle, Skeletal / Q000201:enzymology / Q000473:pathology; D017354:Point Mutation; D011507:Proteinuria / Q000097:blood / Q000235:genetics / Q000473:pathology; D000608:Renal Aminoacidurias / Q000097:blood / Q000235:genetics / Q000473:pathology; D017422:Sequence Analysis, DNA; D014451:Ubiquinone / Q000031:analogs & derivatives* / Q000097:blood / Q000172:deficiency* / Q000235:genetics
chemical_list: D014451:Ubiquinone; D019883:Alkyl and Aryl Transferases; C021386:4-hydroxybenzoate polyprenyltransferase; C024989:coenzyme Q10