title: Respiratory-chain deficiency presenting as diffuse mesangial sclerosis with NPHS3 mutation.
abstract: Renal manifestations of mitochondrial cytopathies have been described, but nephrotic syndrome with respiratory-chain disorders have been described extremely rarely. We report a 9-month-old boy with a mitochondrial cytopathy preceded by a 2-month history of steroid-resistant nephrotic syndrome. Percutaneous renal biopsy revealed diffuse mesangial sclerosis, and mutational analysis was compatible with PLCE1 mutation. However, electron microscopic findings of renal tissue, sensorineural hearing loss, and other ocular and neurologic findings led us to suspect mitochondrial cytopathy. Muscle tissue analysis showed a deficiency of the respiratory chain complex IV. The clinical presentation of our patient is not typical for primary cytochrome oxidase (COX) deficiency but showed similarities with patients carrying AR mutations in COX10. This was the first case in the literature with both PLCE1 mutation and COX deficiency. We could not identify pathogenic mutations in the COX10 gene, suggesting that PLCE1 deficiency could be the cause of the secondary deficiency of COX. Another, more likely, possibility is that the mitochondriopathy phenotype is caused by another mutation homozygous by descent in a yet unidentified recessive gene.
authors.affiliation: Department of Pediatric Nephrology, Baskent University, Ankara, Turkey. esrabaskin@yahoo.com
authors.forename: Esra
authors.initials: E
authors.lastname: Baskin
authors.forename: Umut
authors.initials: U
authors.lastname: Selda Bayrakci
authors.forename: Füsun
authors.initials: F
authors.lastname: Alehan
authors.forename: Handan
authors.initials: H
authors.lastname: Ozdemir
authors.forename: Ayse
authors.initials: A
authors.lastname: Oner
authors.forename: Rita
authors.initials: R
authors.lastname: Horvath
authors.forename: Virginia
authors.initials: V
authors.lastname: Vega-Warner
authors.forename: Friedhelm
authors.initials: F
authors.lastname: Hildebrandt
authors.forename: Fatih
authors.initials: F
authors.lastname: Ozaltin
mesh_terms: D019883:Alkyl and Aryl Transferases / Q000172:deficiency / Q000235:genetics*; D001706:Biopsy; D030401:Cytochrome-c Oxidase Deficiency / Q000150:complications / Q000175:diagnosis* / Q000201:enzymology / Q000235:genetics / Q000628:therapy; D004252:DNA Mutational Analysis; D003576:Electron Transport Complex IV; D020022:Genetic Predisposition to Disease; D006801:Humans; D007223:Infant; D008297:Male; D008565:Membrane Proteins / Q000172:deficiency / Q000235:genetics*; D009154:Mutation; D009404:Nephrotic Syndrome / Q000175:diagnosis* / Q000201:enzymology / Q000235:genetics / Q000628:therapy; D010641:Phenotype; D054801:Phosphoinositide Phospholipase C / Q000235:genetics*; D012598:Sclerosis / Q000175:diagnosis* / Q000201:enzymology / Q000235:genetics / Q000628:therapy
chemical_list: D008565:Membrane Proteins; C490115:COX10 protein, human; D003576:Electron Transport Complex IV; D019883:Alkyl and Aryl Transferases; D054801:Phosphoinositide Phospholipase C; C423320:phospholipase C epsilon