Medullary sponge kidney associated with primary distal renal tubular acidosis and mutations of the H+-ATPase genes

Nephrol Dial Transplant. 2009 Sep;24(9):2734-8. doi: 10.1093/ndt/gfp160. Epub 2009 Apr 13.

Abstract

Background: Medullary sponge kidney (MSK) is a rare congenital disease characterized by diffuse ectasia or dilation of precalyceal collecting tubules. Although its pathogenesis is unknown, the association with various congenital diseases suggests that it could be a developmental disorder. In addition to the typical clinical features of nephrocalcinosis and urolithiasis, patients with MSK show tubular function defects of acidification and concentration. These are considered to be secondary to morphological changes of collecting tubules. Primary distal renal tubular acidosis (dRTA) is a rare genetic disease caused by mutations in different genes involved in the secretion of H(+) ions in the intercalated cells of the collecting duct required for final excretion of fixed acids. Both autosomal dominant and autosomal recessive forms have been described, the latter is also associated with sensorineural hearing loss.

Methods and results: We report two patients presenting with dRTA, late sensorineural hearing loss and MSK, in whom molecular investigations demonstrated the presence of mutations of the H(+) proton pump ATP6V1B1 and ATP6V0A4 genes.

Conclusions: These observations, including a previous description of a similar case in the literature, indicate that MSK could be a consequence of the proton pump defect, thus can potentially provide new insights into the pathogenesis of MSK.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acidosis, Renal Tubular / enzymology
  • Acidosis, Renal Tubular / genetics*
  • Acidosis, Renal Tubular / pathology*
  • Adolescent
  • Adult
  • Base Sequence
  • DNA / genetics
  • DNA Mutational Analysis
  • Female
  • Hearing Loss, Sensorineural / genetics
  • Humans
  • Male
  • Medullary Sponge Kidney / congenital
  • Medullary Sponge Kidney / enzymology
  • Medullary Sponge Kidney / genetics*
  • Medullary Sponge Kidney / pathology*
  • Mutation*
  • Proton-Translocating ATPases / genetics*
  • Syndrome
  • Vacuolar Proton-Translocating ATPases / genetics

Substances

  • ATP6V1B1 protein, human
  • DNA
  • ATP6V0A4 protein, human
  • Vacuolar Proton-Translocating ATPases
  • Proton-Translocating ATPases