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Published January 1, 2016 | Version v1
Journal article Open

ADCK4-Associated Glomerulopathy Causes Adolescence-Onset FSGS

Creators

  • 1. Hacettepe Univ, Fac Med, Dept Pediat Nephrol, Nephrogenet Lab, TR-06100 Ankara, Turkey
  • 2. Paris Descartes Univ, Bioinformat Platform, Imagine Inst, Paris, France
  • 3. Ctr Pediat & Adolescent Med, Div Pediat Nephrol, Heidelberg, Germany
  • 4. Heidelberg Univ, Inst Med Biometry & Informat, Heidelberg, Germany
  • 5. Hacettepe Univ, Fac Med, Dept Pediat Pathol, TR-06100 Ankara, Turkey
  • 6. Hacettepe Univ, Fac Med, Dept Histol & Embryol, TR-06100 Ankara, Turkey
  • 7. Hacettepe Univ, Fac Med, Dept Nephrol, TR-06100 Ankara, Turkey
  • 8. Akdeniz Univ, Fac Med, Dept Surg, TR-07058 Antalya, Turkey
  • 9. Ege Univ, Fac Med, Dept Pediat Nephrol, Izmir, Turkey
  • 10. Cukurova Univ, Dept Pediat Nephrol, Adana, Turkey
  • 11. Istanbul Univ, Istanbul Fac Med, Dept Pediat Nephrol, Istanbul, Turkey
  • 12. Gaziantep Univ, Fac Med, Dept Pediat Nephrol, Gaziantep, Turkey
  • 13. Great Onnond St Hosp Children NHS Fdn Trust, Renal Unit, London, England
  • 14. Biosci Inst Med Diagnost GmbH, Ctr Human Genet, Ingelheim, Germany
  • 15. Hotel Dieu France, Dept Pediat & Pediat Nephrol, Beirut, Lebanon

Description

Hereditary defects of coenzyme Q(10) 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.

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