Familial hypomagnesaemia with hypercalciuria and nephrocalcinosis: clinical and
molecular characteristics
#MMPMID26613020
Claverie-Martin F
Clin Kidney J
2015[Dec]; 8
(6
): 656-64
PMID26613020
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Familial hypomagnesaemia with hypercalciuria and nephrocalcinosis (FHHNC) is an
autosomal-recessive renal tubular disorder characterized by excessive urinary
losses of magnesium and calcium, bilateral nephrocalcinosis and progressive
chronic renal failure. Presentation with FHHNC symptoms generally occurs early in
childhood or before adolescence. At present, the only therapeutic option is
supportive and consists of oral magnesium supplementation and thiazide diuretics.
However, neither treatment seems to have a significant effect on the levels of
serum magnesium or urine calcium or on the decline of renal function. In
end-stage renal disease patients, renal transplantation is the only effective
approach. This rare disease is caused by mutations in the CLDN16 or CLDN19 genes.
Patients with mutations in CLDN19 also present severe ocular abnormalities such
as myopia, nystagmus and macular colobamata. CLDN16 and CLDN19 encode the
tight-junction proteins claudin-16 and claudin-19, respectively, which are
expressed in the thick ascending limb of Henle's loop and form an essential
complex for the paracellular reabsorption of magnesium and calcium. Claudin-19 is
also expressed in retinal epithelium and peripheral neurons. Research studies
using mouse and cell models have generated significant advances on the
understanding of the pathophysiology of FHHNC. A recent finding has established
that another member of the claudin family, claudin-14, plays a key regulatory
role in paracellular cation reabsorption by inhibiting the claudin-16-claudin-19
complex. Furthermore, several studies on the molecular and cellular consequences
of disease-causing CLDN16 and CLDN19 mutations have provided critical information
for the development of potential therapeutic strategies.
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