title: ADCK4-Associated Glomerulopathy Causes Adolescence-Onset FSGS.
abstract: Hereditary defects of coenzyme Q10 biosynthesis cause steroid-resistant nephrotic syndrome (SRNS) as part of multiorgan involvement but may also contribute to isolated SRNS. Here, we report 26 patients from 12 families with recessive mutations in ADCK4. Mutation detection rate was 1.9% among 534 consecutively screened cases. Patients with ADCK4 mutations showed a largely renal-limited phenotype, with three subjects exhibiting occasional seizures, one subject exhibiting mild mental retardation, and one subject exhibiting retinitis pigmentosa. ADCK4 nephropathy presented during adolescence (median age, 14.1 years) with nephrotic-range proteinuria in 44% of patients and advanced CKD in 46% of patients at time of diagnosis. Renal biopsy specimens uniformly showed FSGS. Whereas 47% and 36% of patients with mutations in WT1 and NPHS2, respectively, progressed to ESRD before 10 years of age, ESRD occurred almost exclusively in the second decade of life in ADCK4 nephropathy. However, CKD progressed much faster during adolescence in ADCK4 than in WT1 and NPHS2 nephropathy, resulting in similar cumulative ESRD rates (>85% for each disorder) in the third decade of life. In conclusion, ADCK4-related glomerulopathy is an important novel differential diagnosis in adolescents with SRNS/FSGS and/or CKD of unknown origin.
authors.affiliation: Nephrogenetics Laboratory, Department of Pediatric Nephrology, Hacettepe University Faculty of Medicine, Ankara, Turkey;
authors.forename: Emine
authors.initials: E
authors.lastname: Korkmaz
authors.affiliation: Division of Pediatric Nephrology, Center for Pediatrics and Adolescent Medicine, Heidelberg, Germany; Department of Biology and Genetics, Medical University of Gdansk, Gdansk, Poland; b.lipska@gumed.edu.pl fozaltin@hacettepe.edu.tr.
authors.forename: Beata S
authors.initials: BS
authors.lastname: Lipska-Ziętkiewicz
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM) Unité mixte de recherche (UMR) U1163, Laboratory of Hereditary Kidney Diseases, Paris, France; Université Paris Descartes, Sorbonne Paris Cité, Imagine Institute, Paris, France; Department of Pediatric Nephrology, Necker Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France;
authors.forename: Olivia
authors.initials: O
authors.lastname: Boyer
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM) Unité mixte de recherche (UMR) U1163, Laboratory of Hereditary Kidney Diseases, Paris, France; Université Paris Descartes, Sorbonne Paris Cité, Imagine Institute, Paris, France;
authors.forename: Olivier
authors.initials: O
authors.lastname: Gribouval
authors.affiliation: Paris Descartes University Bioinformatics Platform, Imagine Institute, Paris, France;
authors.forename: Cecile
authors.initials: C
authors.lastname: Fourrage
authors.affiliation: Division of Pediatric Nephrology, Center for Pediatrics and Adolescent Medicine, Heidelberg, Germany;
authors.forename: Mansoureh
authors.initials: M
authors.lastname: Tabatabaei
authors.affiliation: Institute of Medical Biometry and Informatics, University of Heidelberg, Heidelberg, Germany;
authors.forename: Sven
authors.initials: S
authors.lastname: Schnaidt
authors.affiliation: Departments of Pediatric Pathology.
authors.forename: Safak
authors.initials: S
authors.lastname: Gucer
authors.affiliation: Histology and Embryology, and.
authors.forename: Figen
authors.initials: F
authors.lastname: Kaymaz
authors.affiliation: Nephrology, Hacettepe University Faculty of Medicine, Ankara, Turkey;
authors.forename: Mustafa
authors.initials: M
authors.lastname: Arici
authors.affiliation: Department of Surgery, Akdeniz University Faculty of Medicine, Antalya, Turkey;
authors.forename: Ayhan
authors.initials: A
authors.lastname: Dinckan
authors.affiliation: Department of Pediatric Nephrology, Ege University Medical Faculty, Bornova, Izmir, Turkey;
authors.forename: Sevgi
authors.initials: S
authors.lastname: Mir
authors.affiliation: Department of Pediatric Nephrology, Cukurova University, Adana, Turkey;
authors.forename: Aysun K
authors.initials: AK
authors.lastname: Bayazit
authors.affiliation: Department of Pediatric Nephrology, Istanbul Medical Faculty, University of Istanbul, Capa, Istanbul, Turkey;
authors.forename: Sevinc
authors.initials: S
authors.lastname: Emre
authors.affiliation: Department of Pediatric Nephrology, Gaziantep University Medical Faculty, Gaziantep, Turkey;
authors.forename: Ayse
authors.initials: A
authors.lastname: Balat
authors.affiliation: Renal Unit, Great Ormond Street Hospital for Children NHS Foundation Trust, London, United Kingdom;
authors.forename: Lesley
authors.initials: L
authors.lastname: Rees
authors.affiliation: Renal Unit, Great Ormond Street Hospital for Children NHS Foundation Trust, London, United Kingdom;
authors.forename: Rukshana
authors.initials: R
authors.lastname: Shroff
authors.affiliation: Bioscientia Institute for Medical Diagnostics GmbH, Center for Human Genetics, Ingelheim, Germany;
authors.forename: Carsten
authors.initials: C
authors.lastname: Bergmann
authors.affiliation: Hotel Dieu de France, Department of Pediatrics and Pediatric Nephrology, Beirut, Lebanon;
authors.forename: Chebl
authors.initials: C
authors.lastname: Mourani
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM) Unité mixte de recherche (UMR) U1163, Laboratory of Hereditary Kidney Diseases, Paris, France; Université Paris Descartes, Sorbonne Paris Cité, Imagine Institute, Paris, France; Department of Genetics, Necker Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France;
authors.forename: Corinne
authors.initials: C
authors.lastname: Antignac
authors.affiliation: Nephrogenetics Laboratory, Department of Pediatric Nephrology, Hacettepe University Faculty of Medicine, Ankara, Turkey; Department of Pediatric Nephrology, Hacettepe University Faculty of Medicine, Ankara, Turkey; and Hacettepe University Center for Biobanking and Genomics, Ankara, Turkey b.lipska@gumed.edu.pl fozaltin@hacettepe.edu.tr.
authors.forename: Fatih
authors.initials: F
authors.lastname: Ozaltin
authors.affiliation: Division of Pediatric Nephrology, Center for Pediatrics and Adolescent Medicine, Heidelberg, Germany;
authors.forename: Franz
authors.initials: F
authors.lastname: Schaefer
mesh_terms: D000293:Adolescent; D017668:Age of Onset; D002648:Child; D002675:Child, Preschool; D005923:Glomerulosclerosis, Focal Segmental / Q000235:genetics*; D006801:Humans; D007223:Infant; D009154:Mutation; D011494:Protein Kinases / Q000235:genetics*
chemical_list: C586096:COQ8B protein, human; D011494:Protein Kinases
keywords: familial nephropathy; focal segmental glomerulosclerosis; genetic renal disease; glomerulopathy; mitochondria