The Fibroblast Growth Factor 23 (FGF23) gene provides instructions for making a protein called FGF23. This protein is necessary in regulating the phosphate levels within the body. We present a case of an adult Caucasian man with persistent hypophosphatemia due to mutation in ENPP1.
Case History: A 34 years old male presented with intermittent muscle pain, cramps and headaches. He also noticed episodic breathlessness and irritability. He had no history of diarrhoea and he was not on any medications. Blood tests showed persistently low phosphate and his 24 h urinary phosphate excretion was high. His calcium and PTH was normal. He had normal bone densitometry. He had no family history of any illness. He had a genetic test, found a pathogenic variant in the ENPP1 gene c.2375A>G p. (Asn792Ser). This variant has been reported before with other pathogenic variants in patients with hypophosphataemic rickets and infantile arterial calcification.
Discussion: Phosphate levels are controlled in large part by the kidneys. FGF23 signals the kidneys to stop reabsorbing phosphate into the bloodstream. FGF23 also helps to determine the absorption of phosphate by the intestines and plays a role in regulating vitamin D. At least three mutations in the FGF23 gene have been found to cause a rare form of hereditary hypophosphatemic rickets. This is described as autosomal dominant hypophosphatemic rickets (XLH). FGF23 loss-of-function mutations also causes familial hyperphosphatemic tumoral calcinosis (TC), The mutations cause overactivity of FGF23 resulting in decreased phosphate reabsorption by the kidneys, leading to hypophosphatemia. A combination of active vitamin D and phosphate salts is the current medical therapy. This therapy has certain efficacy and safety associated limitations. Several measures to inhibit FGF23 activity have been considered as possible new treatments for FGF23-related hypophosphatemia. In particular, a humanized monoclonal antibody for FGF23 (Burosumab) is a promising treatment in these patients.