Impaired paracellular ion transport in the loop of Henle causes familial hypomagnesemia with hypercalciuria and nephrocalcinosis.
Familial hypomagnesemia with hypercalciuria and nephrocalcinosis (FHHNC) is a rare tubular disorder caused by mutations in genes coding for tight junction (TJ) proteins. TJs define the paracellular path between adjacent cells and thereby play a pivotal role for the regulation of the paracellular ion permeability of epithelia. The family of TJ proteins comprise a variety of transmembrane proteins, including the claudins. Multiple distinct mutations in the genes for claudin-16 and -19 have been described to be responsible for FHHNC. Both encoded proteins are especially important for the paracellular reabsorption of Mg(2+)  and Ca(2+)  in the thick ascending limb of Henle's loop. Interestingly, in addition to ion disturbances, FHHNC leads to chronic renal failure and may be associated with extrarenal symptoms.
Department of General Pediatrics, University Hospital Münster, Münster, Germany.
Lea
L
Haisch
Martin
M
Konrad
D006801:Humans; D053565:Hypercalciuria / Q000378:metabolism*; D017136:Ion Transport; D008138:Loop of Henle / Q000378:metabolism*; D008274:Magnesium / Q000097:blood*; D009397:Nephrocalcinosis / Q000378:metabolism*
D008274:Magnesium