Hereditary hypophosphatemic rickets, previously known as vitamin D resistant rickets, refers to a genetically heterogeneous group of causes of rickets related to renal phosphate wasting. The disorder is resistant to treatment with vitamin D supplementation.
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Clinical presentation
Children present with abnormally slowed growth. Laboratory findings include low serum phosphate, normal serum calcium, low serum alkaline phosphatase3, and normal to modestly elevated parathyroid hormone. Vitamin D levels are often normal.
Pathology
This group of disorders results from a failure in phosphate reabsorption in the renal tubules. The final common mechanism of most, but not all, of these disorders is elevated levels of the hormone fibroblast growth factor 23 (FGF23), a phosphatonin that inhibits the sodium/phosphate cotransporters in the kidney.
Genetics
Many genetic causes have been implicated 1:
X-linked hypophosphatemic rickets (most common): PHEX mutation
autosomal dominant hypophosphatemic rickets: FGF23 mutation
autosomal recessive hypophosphatemic rickets: DMP1 mutation
McCune-Albright syndrome: GNAS mutation
epidermal nevus syndrome: RAS mutation
hereditary hypophosphatemic rickets with hypercalciuria: SLC34A3 mutation
Radiographic features
Findings are similar to nutritional rickets 2.
Differential diagnosis
Other causes of hypophosphatemic/phosphopenic rickets include
Fanconi syndrome, a generalized proximal tubulopathy that can be acquired or inherited
tumor-induced osteomalacia/rickets, a paraneoplastic syndrome of phosphaturic mesenchymal tumor
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