FGF23 Mutations: What They Are and Why They Matter

Ever wonder why some people develop weird calcium deposits or weak bones for no clear reason? The answer often points to a tiny gene called FGF23. When this gene mutates, it throws off the way your body handles phosphate, a mineral that’s key for bone strength and kidney function.

How FGF23 Mutations Change Phosphate Balance

Under normal conditions, FGF23 acts like a traffic cop, telling the kidneys to dump excess phosphate in the urine. A mutation can either crank up or shut down this signal. When the gene is over‑active, your kidneys throw away too much phosphate, leading to low blood phosphate levels and a condition called autosomal dominant hypophosphatemic rickets (ADHR). On the flip side, a loss‑of‑function mutation stops the signal, causing phosphate to pile up in the blood and resulting in hyperphosphatemic familial tumoral calcinosis (HFTC). Both extremes cause bone pain, muscle weakness, and sometimes visible calcium deposits under the skin.

Spotting the Problem: Symptoms and Diagnosis

If you’re dealing with unexplained bone pain, frequent fractures, or hard lumps near joints, ask your doctor about a possible FGF23 issue. Doctors usually start with blood tests—low phosphate points toward ADHR, while high phosphate hints at HFTC. A urine test checks how much phosphate your kidneys are clearing. If the lab results look off, the next step is genetic testing. A simple cheek‑swab can reveal whether you carry a known FGF23 mutation.

Imaging also helps. X‑rays or CT scans can show the classic calcified masses in HFTC or the bowed bones typical of rickets. Putting all these clues together lets doctors confirm the diagnosis and rule out other causes like kidney disease or vitamin D problems.

Managing FGF23‑Related Disorders

Treatment depends on which side of the phosphate seesaw you fall on. For ADHR, the goal is to raise blood phosphate. Doctors often prescribe oral phosphate supplements and active vitamin D analogs, which help the gut absorb more phosphate. Regular monitoring is key—too much supplement can cause kidney stones.

In HFTC, the strategy flips: you need to lower phosphate. Low‑phosphate diets and phosphate binders, which trap phosphate in the gut, are common tools. Some patients also benefit from drugs that block the FGF23 pathway, though these are still being studied.

Beyond meds, lifestyle tweaks matter. Staying hydrated, avoiding high‑phosphate foods (like certain sodas and processed meats), and keeping an eye on calcium intake can help keep the balance in check. Physical therapy may improve strength and reduce joint stress, especially for those dealing with calcified masses.

Because FGF23 mutations are genetic, family members might also be carriers. Talk to a genetic counselor if a mutation is found in your family—early testing can catch problems before they cause serious bone damage.

Bottom line: FGF23 mutations mess with your phosphate, leading to either too little or too much in the blood. Recognizing the symptoms, getting the right labs, and confirming the gene change are the first steps. With targeted supplements, diet changes, and careful monitoring, most people can manage the condition and keep their bones healthy.