Hypomagnesaemia of hereditary renal origin

Abstract

Cases of hypomagnesaemia of hereditary renal origin represent at least three different congenital disorders of tubular reabsorption of magnesium (Mg). Isolated familial hypomagnesaemia has been reported in a heterogeneous group of patients and an autosomal dominant pattern of inheritance has often been found to be present. Familial hypokalaemia-hypomagnesaemia, inherited as an autosomal recessive trait, has been reported in 17 patients and we now describe 3 additional cases. Hypomagnesaemia is accompanied by hypokalaemia, metabolic alkalosis, hypocalciuria and moderate sodium chloride wasting. Titration of renal Mg reabsorption indicates the presence of a low threshold but a normal Tm. The inherited defect is probably situated at the level of the distal convoluted tubule and mimics the therapeutic effect of thiazides. This condition is frequently confused with Bartter's syndrome. Familial hypomagnesaemia-hypercalciuria, also inherited as an autosomal recessive trait, has been reported in at least 15 patients and we now add 3 new cases. Hypomagnesaemia is always accompanied by hypercalciuria and nephrocalcinosis. Ocular abnormalities such as myopia and horizontal nystagmus are often present. Hypermagnesiuria is of a greater degree than that observed in the previous entity and reflects a low Tm of Mg reabsorption. The defect must be situated at the level of the ascending limb of the loop of Henle and affects the transport of both calcium and Mg but not of sodium and chloride. This condition has not been clearly separated from hereditary distal renal tubular acidosis in the literature.

Biology of claudins

“…The only inherited renal disease attributable to claudin mutations so far is FHHNC, an autosomal recessive disease characterized by renal Mg 2ϩ wasting, hypercalciuria, and nephrocalcinosis (84), which usually leads to chronic renal failure. Rodriguez-Soriano et al (84) first proposed that FHHNC might be due to a defect in tubular reabsorption in the TALH.…”

“…The only inherited renal disease attributable to claudin mutations so far is FHHNC, an autosomal recessive disease characterized by renal Mg 2ϩ wasting, hypercalciuria, and nephrocalcinosis (84), which usually leads to chronic renal failure. Rodriguez-Soriano et al (84) first proposed that FHHNC might be due to a defect in tubular reabsorption in the TALH. This was based on the magnitude of the observed increase in fractional excretion of Mg 2ϩ , which could only be accounted for by a defect in the TALH and the fact that linked transport of Ca 2ϩ and Mg 2ϩ is characteristic of the TALH.…”

Renal tubular function in children and adolescents with Gitelnian's syndrome, the hypocalciuric variant of Bartter's syndrome

“…The present investigation was performed in children and adolescents with Gitelman's syndrome, the hypocalciurica variant of Bartter's syndrome [1][2][3][4][5][6][7][8][9]. The study provides information on three phenomena, one dealing with the mechanisms underlying magnesium deficiency, one dealing with the mechanisms underlying hypocalciuria, and one dealing with the site of the renal tubular dysfunction.…”

“…Patients with this tubulopathy, which is inherited in both dominant and recessive fashions [9], are often asymptomatic, with the exception of muscular weakness and transient episodes of tetany that are sometimes accompanied by abdominal pain, vomiting and fever [1][2][3][4][5][6][7][8][9].…”

“…Since the need for distinguishing between classic Bartter's syndrome and Gitelman's syndrome has been challenged until recently [3][4][5][6][7][8][9], information on renal tubular function in this particular disorder is scanty and based on anecdotal reports [1,2,[4][5][6][7][8] and a retrospective multicentric inquiry [3]. To address this issue, simple renal tubular function studies were performed in 14 patients with Gitelman's syndrome on follow-up at our centres of Pediatric Nephrology.…”