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J Am Soc Nephrol. 2016 Jan;27(1):63-8. doi: 10.1681/ASN.2014121240. Epub 2015 May 12.

ADCK4-Associated Glomerulopathy Causes Adolescence-Onset FSGS.

Author information

1
Nephrogenetics Laboratory, Department of Pediatric Nephrology, Hacettepe University Faculty of Medicine, Ankara, Turkey;
2
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.
3
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;
4
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;
5
Paris Descartes University Bioinformatics Platform, Imagine Institute, Paris, France;
6
Division of Pediatric Nephrology, Center for Pediatrics and Adolescent Medicine, Heidelberg, Germany;
7
Institute of Medical Biometry and Informatics, University of Heidelberg, Heidelberg, Germany;
8
Departments of Pediatric Pathology.
9
Histology and Embryology, and.
10
Nephrology, Hacettepe University Faculty of Medicine, Ankara, Turkey;
11
Department of Surgery, Akdeniz University Faculty of Medicine, Antalya, Turkey;
12
Department of Pediatric Nephrology, Ege University Medical Faculty, Bornova, Izmir, Turkey;
13
Department of Pediatric Nephrology, Cukurova University, Adana, Turkey;
14
Department of Pediatric Nephrology, Istanbul Medical Faculty, University of Istanbul, Capa, Istanbul, Turkey;
15
Department of Pediatric Nephrology, Gaziantep University Medical Faculty, Gaziantep, Turkey;
16
Renal Unit, Great Ormond Street Hospital for Children NHS Foundation Trust, London, United Kingdom;
17
Bioscientia Institute for Medical Diagnostics GmbH, Center for Human Genetics, Ingelheim, Germany;
18
Hotel Dieu de France, Department of Pediatrics and Pediatric Nephrology, Beirut, Lebanon;
19
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;
20
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.

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.

KEYWORDS:

familial nephropathy; focal segmental glomerulosclerosis; genetic renal disease; glomerulopathy; mitochondria

PMID:
25967120
PMCID:
PMC4696579
DOI:
10.1681/ASN.2014121240
[Indexed for MEDLINE]
Free PMC Article

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