Hereditary hypophosphatemic rickets with hypercalciuria is a rare autosomal recessive disorder (OMIM #241530), characterized by decreased renal
phosphate reabsorption that leads to
hypophosphatemia,
rickets, and bone
pain;
hypophosphatemia is believed to stimulate 1,25 dihydroxyvitamin D synthesis which, in turn, results in
hypercalciuria.
Hereditary hypophosphatemic rickets with hypercalciuria is caused by loss-of-function in the type 2c
sodium phosphate cotransporter encoded by the SLC34A3 gene. This report shows a family with a non-previously identified mutation in the SLC34A3 gene and exhibiting mild and different manifestations of HHRH. The probandus had
hypophosphatemia, elevated serum 1,25 dihydroxyvitamin D concentrations, high serum
alkaline phosphatase levels,
hypercalciuria and
nephrocalcinosis. The other members of the family presented some of these alterations: the mother,
hypercalciuria and high 1,25 dihydroxyvitamin D concentrations; the son,
hypercalciuria, high 1,25 dihydroxyvitamin D values and elevated alkaline
phosphatases; the father, high alkaline
phosphatases. The genetic analysis revealed the existence of a single mutation (G78R) in heterozygosis in the SLC34A3 gene in the probandus, her mother and her brother, but not in the father. These findings suggest that he mutation in heterozygosis likely gave rise to a mild phenotype with different penetrance in the three relatives and also indicates that the elevation of 1,25 dihydroxyvitamin D does not result from
hypophosphatemia. Thus, this family raises some issues on the transmission and pathophysiology of
hereditary hypophosphatemic rickets with hypercalciuria.