Hypophosphatemia Genes – What You Need to Know

Low phosphate in the blood can be more than a diet issue – it often runs in families. When a gene that controls phosphate handling is off‑balance, the body can’t keep enough mineral in the bones and teeth. Knowing the genes involved helps you and your doctor choose the right tests and treatments faster.

Main Genes Linked to Low Phosphate

The most common culprit is the PHEX gene. Mutations here cause X‑linked hypophosphatemic rickets, the classic form that shows up in childhood with soft bones and growth problems. Another big player is FGF23. This gene makes a hormone that tells the kidneys to dump phosphate. When it’s over‑active, blood phosphate drops even if you eat enough.

Other genes can cause similar issues. DMP1 mutations lead to autosomal‑recessive hypophosphatemia, often with bone pain and frequent fractures. ENPP1 defects are linked to a rare form that can also affect blood vessels. Finally, SLC34A3 (and its partner SLC34A1) code for kidney transporters; when they don’t work right, the kidneys waste phosphate.

Testing and Managing Genetic Hypophosphatemia

First step is a simple blood test: low serum phosphate plus high alkaline phosphatase points you toward a genetic cause. Your doctor may then order a genetic panel that checks the genes mentioned above. Most labs can do this from a cheek swab or a small blood draw, and results usually come back in a few weeks.

If a mutation is confirmed, treatment focuses on replacing the missing mineral and stopping the hormone that’s causing waste. Standard care includes oral phosphate supplements taken several times a day and active vitamin D (calcitriol) to help absorb the mineral. A newer option is burosumab, an antibody that blocks FGF23. It’s approved for children and adults with PHEX‑related disease and can reduce the need for high‑dose phosphate pills.

Living with a genetic phosphate problem also means watching your diet and staying active. Foods high in phosphate – dairy, nuts, beans, and whole grains – can help, but they’re not a cure on their own. Regular exercise keeps bones strong, but avoid high‑impact sports if your doctor says your bones are fragile.

Follow‑up is key. Your doctor will check blood phosphate, calcium, and kidney function every few months, adjusting doses as you grow or as the condition changes. Many people with the right treatment lead normal lives, but missing a diagnosis can lead to lasting bone deformities.

Bottom line: if you or a family member has unexplained bone pain, short stature, or frequent fractures, ask your doctor about a phosphate panel and genetic testing. Early detection means you can start the right supplements or medication before serious damage occurs.

For more detailed guidance on specific genes, test options, and drug information, explore OCNAT.org’s disease and medication database. It’s a free, trusted source that keeps up with the latest research, so you always have the facts you need to make the best health decisions.