title: Focal segmental glomerulosclerosis and medullary nephrocalcinosis in children with ADCK4 mutations.
abstract: Mutations in the AarF domain containing kinase 4 gene (ADCK4), one of the novel genes causing steroid-resistant nephrotic syndrome (SRNS), usually manifest as isolated adolescent-onset focal segmental glomerulosclerosis (FSGS). ADCK4 interacts with components of the coenzyme Q10 (CoQ10) biosynthesis pathway.
  
  
  
  The incidence and phenotypes of patients with ADCK4 mutations were investigated in a cohort of Korean pediatric patients with SRNS.
  
  
  
  Among the 53 patients enrolled in the study the incidence of ADCK4-associated FSGS was 7.5% (n = 4) in children aged 5 years and older with multidrug-resistant FSGS. Two additional patients were included for phenotype analyses, one detected by family screening and the other with cyclosporine-responsive FSGS. These six patients presented proteinuria without overt nephrotic syndrome at a median age of 110 (range 60-153) months, of whom five progressed to end-stage renal disease within a median period of 46 (range 36-79) months after onset. Renal biopsies revealed mitochondrial abnormalities in podocytes and tubular cells of all patients. Notably, all patients showed accompanying medullary nephrocalcinosis. None of the patients showed other extrarenal manifestations.
  
  
  
  ADCK4 mutations should be considered in older children presenting with steroid resistant FSGS. An early diagnosis of ADCK4 mutations is essential because the condition is treatable with CoQ10 supplementation at an early stage. The association with medullary nephrocalcinosis may be an additional diagnostic indicator.
authors.affiliation: Department of Pediatrics, Seoul National University Children's Hospital, 101 Daehak-Ro, Jongno-Gu, Seoul, 03080, South Korea.
authors.forename: Eujin
authors.initials: E
authors.lastname: Park
authors.affiliation: Department of Pediatrics, Seoul National University Children's Hospital, 101 Daehak-Ro, Jongno-Gu, Seoul, 03080, South Korea.|Research Coordination Center for Rare Diseases, Seoul National University Hospital, Seoul, 03080, South Korea.
authors.forename: Hee Gyung
authors.initials: HG
authors.lastname: Kang
authors.affiliation: Department of Radiology, Seoul National University College of Medicine, Seoul, 03080, South Korea.
authors.forename: Young Hun
authors.initials: YH
authors.lastname: Choi
authors.affiliation: Department of Pathology, Seoul National University Hospital, Seoul, 03080, South Korea.
authors.forename: Kyoung Bun
authors.initials: KB
authors.lastname: Lee
authors.affiliation: Department of Pathology, Seoul National University Hospital, Seoul, 03080, South Korea.|Kidney Research Institute, Medical Research Center, Seoul National University College of Medicine, Seoul, 03080, South Korea.
authors.forename: Kyung Chul
authors.initials: KC
authors.lastname: Moon
authors.affiliation: Department of Pathology, Yonsei University College of Medicine, Seoul, South Korea.
authors.forename: Hyeon Joo
authors.initials: HJ
authors.lastname: Jeong
authors.affiliation: Kidney and Vascular Pathology, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan.
authors.forename: Michio
authors.initials: M
authors.lastname: Nagata
authors.affiliation: Department of Pediatrics, Seoul National University Children's Hospital, 101 Daehak-Ro, Jongno-Gu, Seoul, 03080, South Korea. cheonghi@snu.ac.kr.|Research Coordination Center for Rare Diseases, Seoul National University Hospital, Seoul, 03080, South Korea. cheonghi@snu.ac.kr.|Kidney Research Institute, Medical Research Center, Seoul National University College of Medicine, Seoul, 03080, South Korea. cheonghi@snu.ac.kr.
authors.forename: Hae Il
authors.identifier: 0000-0001-7556-1265
authors.initials: HI
authors.lastname: Cheong
mesh_terms: D002648:Child; D018450:Disease Progression; D005260:Female; D056726:Genetic Association Studies; D005923:Glomerulosclerosis, Focal Segmental / Q000453:epidemiology* / Q000235:genetics / Q000473:pathology; D006801:Humans; D015994:Incidence; D007676:Kidney Failure, Chronic / Q000453:epidemiology* / Q000235:genetics; D007723:Korea / Q000453:epidemiology; D008297:Male; D009154:Mutation; D009397:Nephrocalcinosis / Q000453:epidemiology* / Q000235:genetics / Q000473:pathology; D009404:Nephrotic Syndrome / Q000151:congenital* / Q000453:epidemiology / Q000235:genetics / Q000473:pathology; D011494:Protein Kinases / Q000235:genetics*
chemical_list: C586096:COQ8B protein, human; D011494:Protein Kinases
keywords: ADCK4 mutation; Coenzyme Q10 deficiency; Focal segmental glomerulosclerosis; Medullary nephrocalcinosis; Steroid-resistant nephrotic syndrome