Dominant hypophosphatemia with nephrolithiasis or osteoporosis

Dominant hypophosphatemia with nephrolithiasis or osteoporosis (also known as hypophosphatemic nephrolithiasis/osteoporosis type 1 or type 2) is a rare inherited disorder of phosphate metabolism caused by mutations in genes that regulate renal phosphate reabsorption, most notably SLC34A1 (encoding the sodium-phosphate cotransporter NaPi-IIa) or SLC34A3 (encoding NaPi-IIc). The condition is characterized by renal phosphate wasting, leading to hypophosphatemia (low blood phosphate levels). This phosphate imbalance primarily affects the kidneys and skeletal system. Patients typically present in adulthood with recurrent kidney stones (nephrolithiasis), often composed of calcium phosphate, and/or reduced bone mineral density leading to osteoporosis and increased fracture risk. Laboratory findings include low serum phosphate, increased urinary phosphate excretion, elevated or inappropriately normal 1,25-dihydroxyvitamin D levels, and sometimes hypercalciuria. Unlike X-linked hypophosphatemia, patients with this condition generally do not develop rickets or significant skeletal deformities in childhood. Management focuses on addressing the complications of phosphate wasting. Oral phosphate supplementation may be considered to correct hypophosphatemia, though care must be taken as it can worsen hypercalciuria and kidney stone formation. Thiazide diuretics may be used to reduce urinary calcium excretion and prevent nephrolithiasis. Adequate hydration and dietary modifications are also recommended. Bone health is monitored with periodic bone density assessments, and bisphosphonates or other osteoporosis treatments may be employed when significant bone loss is present. Genetic counseling is recommended for affected families given the autosomal dominant inheritance pattern.

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