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Pediatric Nephrology

, Volume 32, Issue 9, pp 1547–1554 | Cite as

Focal segmental glomerulosclerosis and medullary nephrocalcinosis in children with ADCK4 mutations

  • Eujin Park
  • Hee Gyung Kang
  • Young Hun Choi
  • Kyoung Bun Lee
  • Kyung Chul Moon
  • Hyeon Joo Jeong
  • Michio Nagata
  • Hae Il Cheong
Original Article

Abstract

Background

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.

Methods

The incidence and phenotypes of patients with ADCK4 mutations were investigated in a cohort of Korean pediatric patients with SRNS.

Results

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.

Conclusions

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.

Keywords

ADCK4 mutation Coenzyme Q10 deficiency Focal segmental glomerulosclerosis Medullary nephrocalcinosis Steroid-resistant nephrotic syndrome 

Notes

Acknowledgments

This study was supported by a grant (HI12C0014) from the Korean Health Technology R&D Project, Ministry of Health & Welfare, Republic of Korea.

Compliance with ethical standards

Disclosure

None.

Ethical compliance

This study was approved by the Institutional Review Board of the Seoul National University Hospital. Before the study, informed consent was obtained from all patients or their parents.

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Copyright information

© IPNA 2017

Authors and Affiliations

  1. 1.Department of PediatricsSeoul National University Children’s HospitalSeoulSouth Korea
  2. 2.Research Coordination Center for Rare DiseasesSeoul National University HospitalSeoulSouth Korea
  3. 3.Department of RadiologySeoul National University College of MedicineSeoulSouth Korea
  4. 4.Department of PathologySeoul National University HospitalSeoulSouth Korea
  5. 5.Kidney Research Institute, Medical Research CenterSeoul National University College of MedicineSeoulSouth Korea
  6. 6.Department of PathologyYonsei University College of MedicineSeoulSouth Korea
  7. 7.Kidney and Vascular Pathology, Faculty of MedicineUniversity of TsukubaTsukubaJapan

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