HELIX syndrome in childhood. A claudinopathy with a salt-wasting tubulopathy phenotype with hypermagnesemia

The thick ascending limb of the loop of Henle (TAL) reabsorbs approximately 30% of filtered NaCl through two mechanisms: transepithelial and paracellular reabsorption. The latter is carried out through a class of tight junction proteins known as claudins. A mutation in the gene encoding claudin-10 causes a rare salt-wasting tubular disorder with hypokalemic metabolic alkalosis. However, unlike Bartter syndrome and Gitelman disease, it usually presents with hypermagnesemia and extrarenal manifestations such as xerostomia, alacrima, and hypohidrosis with ichthyosis, known by the acronym HELIX syndrome.