title: COQ2 nephropathy: a newly described inherited mitochondriopathy with primary renal involvement.
abstract: Primary coenzyme Q(10) (CoQ(10)) deficiency includes a group of rare autosomal recessive disorders primarily characterized by neurological and muscular symptoms. Rarely, glomerular involvement has been reported. The COQ2 gene encodes the para-hydroxybenzoate-polyprenyl-transferase enzyme of the CoQ(10) synthesis pathway. We identified two patients with early-onset glomerular lesions that harbored mutations in the COQ2 gene. The first patient presented with steroid-resistant nephrotic syndrome at the age of 18 months as a result of collapsing glomerulopathy, with no extrarenal symptoms. The second patient presented at five days of life with oliguria, had severe extracapillary proliferation on renal biopsy, rapidly developed end-stage renal disease, and died at the age of 6 months after a course complicated by progressive epileptic encephalopathy. Ultrastructural examination of renal specimens from these cases, as well as from two previously reported patients, showed an increased number of dysmorphic mitochondria in glomerular cells. Biochemical analyses demonstrated decreased activities of respiratory chain complexes [II+III] and decreased CoQ(10) concentrations in skeletal muscle and renal cortex. In conclusion, we suggest that inherited COQ2 mutations cause a primary glomerular disease with renal lesions that vary in severity and are not necessarily associated with neurological signs. COQ2 nephropathy should be suspected when electron microscopy shows an increased number of abnormal mitochondria in podocytes and other glomerular cells.
authors.affiliation: Divisions of Pathology , Department of Laboratory Medicine, Bambino Gesù Children's Hospital and Research Institute, Rome, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Diomedi-Camassei
authors.forename: Silvia
authors.initials: S
authors.lastname: Di Giandomenico
authors.forename: Filippo M
authors.initials: FM
authors.lastname: Santorelli
authors.forename: Gianluca
authors.initials: G
authors.lastname: Caridi
authors.forename: Fiorella
authors.initials: F
authors.lastname: Piemonte
authors.forename: Giovanni
authors.initials: G
authors.lastname: Montini
authors.forename: Gian Marco
authors.initials: GM
authors.lastname: Ghiggeri
authors.forename: Luisa
authors.initials: L
authors.lastname: Murer
authors.forename: Laura
authors.initials: L
authors.lastname: Barisoni
authors.forename: Anna
authors.initials: A
authors.lastname: Pastore
authors.forename: Andrea Onetti
authors.initials: AO
authors.lastname: Muda
authors.forename: Maria Luisa
authors.initials: ML
authors.lastname: Valente
authors.forename: Enrico
authors.initials: E
authors.lastname: Bertini
authors.forename: Francesco
authors.initials: F
authors.lastname: Emma
mesh_terms: D058186:Acute Kidney Injury / Q000235:genetics* / Q000473:pathology; D019883:Alkyl and Aryl Transferases / Q000235:genetics*; D003067:Coenzymes / Q000172:deficiency; D045222:Electron Transport Chain Complex Proteins / Q000378:metabolism; D006801:Humans; D007223:Infant; D007668:Kidney / Q000378:metabolism / Q000473:pathology*; D008297:Male; D028361:Mitochondrial Diseases / Q000235:genetics* / Q000473:pathology; D018482:Muscle, Skeletal / Q000378:metabolism; D020125:Mutation, Missense; D009404:Nephrotic Syndrome / Q000235:genetics* / Q000473:pathology; D014451:Ubiquinone / Q000031:analogs & derivatives / Q000172:deficiency
chemical_list: D003067:Coenzymes; D045222:Electron Transport Chain Complex Proteins; D014451:Ubiquinone; D019883:Alkyl and Aryl Transferases; C021386:4-hydroxybenzoate polyprenyltransferase; C024989:coenzyme Q10