Familial hypomagnesemia-hypercalciuria in 2 siblings

Familial hypomagnesemia-hypercalciuria with nephrocalcinosis and renal insu fficiency in childhood is a rarely described disease. Two siblings of consa nguineous Tunesian parents (first cousins), a 2-year-old boy and a 4-year-o ld girl presented with renal insufficiency and severe bilateral nephrocalci nosis. Both were found to have decreased serum and intracellular magnesium concentrations, increased urinary excretion of magnesium and calcium, mild glomerular and severe tubular proteinuria and low citrate excretion in urin e. Pathological biochemical findings and the severity of nephrocalcinosis o f the boy compared to findings of the sister were strongly marked. Histolog y of the boy's kidney showed severe medullary nephrocalcinosis, tubular atr ophy, focal lymphoplasmacellulary infiltration, focal cortical fibrosis, im mature glomerula, segmental and global glomerulosclerosis. Subsequent mutat ion analysis revealed a homozygous frameshift mutation in the gene paracell in-1 in both affected individuals. Therapy consisted of sodium bicarbonate, cholecalciferol, calcitriol, hydrochlorothiazide, citrate salts and oral m agnesium administration. Hypercalciuria decreased in both children by thera py with thiazide diuretics, but hypomagnesemia was unresponsive to magnesiu m administration. After a 32-month follow-up the boy commenced hemodialysis at the age of 5 years, whereas his sister showed no decline in renal funct ion.