Hypophosphatemia nephrolithiasis osteoporosis type 1 (NPHLOP1)

(OMIM phenotype number #612286)

Hypophosphatemia nephrolithiasis osteoporosis type 1 (NPHLOP1) is caused by heterozygous mutation in the SLC34A1 gene. The gene encodes the protein for the type 2a sodium–phosphate cotransporter (NPT2a), which resides in the apical membrane of renal proximal tubular cells. Phosphate homeostasis is principally regulated by the kidney, modulating urinary phosphate excretion. SLC34A1 mutations have been identified in few patients with impairment in renal phosphate reabsorption, resulting in hypophosphatemia, associated with urolithiasis or bone demineralization of variable severity in both sexes.

Gene

SLC34A1 (NPT2a) gene, 5q35.3 (OMIM gene/locus number #182309).

Phenotype

Kidney stones, nephocalcinosis, osteoporosis.

Main biochemical alterations

High Ur P, low Pi, low renal TmP/GFR, normal calcium, high Ur Ca, low/normal PTH, normal 25 OH D, high 1,25(OH)2D, high bone ALP, normal Ca, and normal intact FGF23.

References

  1. Prié D, Huart V, Bakouh N et al. Nephrolithiasis and osteoporosis associated with hypophosphatemia caused by mutations in the type 2a sodium-phosphate cotransporter. N Engl J Med. 2002 Sep 26;347(13):983-91.
  2. Prié D, Beck L, Friedlander G, et al. Sodium-phosphate cotransporters, nephrolithiasis and bone demineralization. Curr Opin Nephrol Hypertens. 2004 Nov;13(6):675-81.
  3. Prié D, Beck L, Silve C, et al. Hypophosphatemia and calcium nephrolithiasis. Nephron Exp Nephrol. 2004;98(2):e50-4.
  4. Murer H, Hernando N, Forster I, et al. Proximal tubular phosphate reabsorption: molecular mechanisms. Physiol Rev. 2000 Oct;80(4):1373-409.
  5. Masi L, Agnusdei D, Bilezikian J et al. Taxonomy of rare genetic metabolic bone disorders. Osteoporos Int. 2015 Jun 13.
  6. http://www.omim.org