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


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.
Carboni
Ilaria
I
Department of Clinical Pathophysiology, University of Florence, Italy.
Andreucci
Elena
E
Caruso
Maria R
MR
Ciccone
Roberto
R
Zuffardi
Orsetta
O
Genuardi
Maurizio
M
Pela
Ivana
I
Giglio
Sabrina
S
D000141:Acidosis, Renal Tubular / Q000201:enzymology / Q000235:genetics* / Q000473:pathology*; D000293:Adolescent; D000328:Adult; D001483:Base Sequence; D004247:DNA / Q000235:genetics; D004252:DNA Mutational Analysis; D005260:Female; D006319:Hearing Loss, Sensorineural / Q000235:genetics; D006801:Humans; D008297:Male; D007691:Medullary Sponge Kidney / Q000151:congenital / Q000201:enzymology / Q000235:genetics* / Q000473:pathology*; D009154:Mutation; D006180:Proton-Translocating ATPases / Q000235:genetics*; D013577:Syndrome; D025262:Vacuolar Proton-Translocating ATPases / Q000235:genetics
C509766:ATP6V1B1 protein, human; D004247:DNA; C490181:ATP6V0A4 protein, human; D025262:Vacuolar Proton-Translocating ATPases; D006180:Proton-Translocating ATPases