This Rare Disease Makes Bones as Soft as Jelly – But Caused by a Single Gene

This Rare Disease Makes Bones as Soft as Jelly – But Caused by a Single Gene. ADHR is a rare genetic disease where the kidneys excrete too much phosphate, causing soft and brittle bones, bone pain, and tooth abscesses. Interestingly, it can appear at any time from childhood to young adulthood. More astonishingly, current treatments using human antibodies can reverse the condition. Let's uncover the mystery of this enigmatic disease.. When Bones Become as Soft as Tissue Imagine your bones – which should be hard and strong – suddenly becoming soft, fragile, and prone to breaking. Sounds like a nightmare, right? But for patients with Autosomal Dominant Hypophosphatemic Rickets ADHR , this is their reality. ADHR is a very rare genetic disease where the body loses too much phosphate through urine. Phosphate is essential for building strong bones. When it leaks out like a broken pipe, the bones cannot get enough minerals, resulting in weakness and easy injury. Worse still, this disease affects both men and women equally, and symptoms can appear anytime – from childhood to adulthood. The FGF23 Gene: The Real Culprit Behind the Chaos What makes ADHR different from other bone diseases? The answer is one gene: FGF23. This gene produces a protein called fibroblast growth factor 23 FGF23 . In a normal body, FGF23 functions like a traffic controller – it tells the kidneys when to excrete phosphate and when to retain it. However, in ADHR patients, a mutation in the FGF23 gene causes the protein to become 'power-hungry'. It instructs the kidneys to excrete excessive phosphate, even though the body is severely deficient. As a result, phosphate levels in the blood drop dramatically – doctors call this condition hypophosphatemia . Most intriguingly, vitamin D levels in the blood appear normal, even though the bones look like crumbling limestone. This distinguishes ADHR from other types of rickets, where vitamin D levels are usually low. Bone Pain, Tooth Abscesses, and More Symptoms ADHR patients do not necessarily have bent bones at birth. Some appear healthy until adulthood, then suddenly experience severe bone pain. This pain often occurs in the hips, knees, and ankles – like being stabbed by a thousand needles. Bones become easily fractured even with minor impacts. More surprisingly, many patients suffer from recurring tooth abscesses. This is because the lack of phosphate weakens the enamel, allowing bacteria to enter easily. For children, growth is often stunted, and legs may take on an X or O shape. Sometimes, these symptoms can subside on their own as the patient ages – the kidneys suddenly 'learn' to reduce phosphate excretion. But don't be deceived, the condition can return at any time. More Than One Type of Rickets: Why Accurate Diagnosis Is Important Many people hear 'rickets' and immediately think of vitamin D deficiency. But ADHR is different – it is an inherited form of hypophosphatemic rickets. In fact, there are at least nine other gene mutations that can cause similar conditions, including the most well-known, X-linked hypophosphatemic rickets XLH . However, ADHR is special because it is autosomal dominant – meaning only one copy of the mutated gene from one parent is enough for the child to inherit the disease. That is why molecular diagnosis is extremely important. Doctors must perform genetic tests to confirm whether it is ADHR, XLH, or another type. Because treatment may differ. If misdiagnosed, patients could receive ineffective treatment, wasting time and money. From Supplements to Antibodies: The Revolution in ADHR Treatment In the past, the main treatment for ADHR was phosphate supplements and active vitamin D. Patients had to take phosphate pills multiple times a day, sometimes up to 5-6 times. However, this treatment is not perfect – it can cause diarrhea, stomach pain, and the risk of kidney stones. Worse still, it does not address the root cause. However, since 2019, a modern miracle has emerged: burosumab . This is a human monoclonal antibody specifically designed to block FGF23. By blocking the main culprit, the kidneys stop excreting excess phosphate, and phosphate levels in the blood return to normal. In a clinical study, children with XLH who were given burosumab showed significant improvement in bone formation and reduced pain. Although specific studies on ADHR are limited, the same principle is expected to be effective. Now, ADHR patients have a new hope – treatment that not only relieves symptoms but also corrects the disease mechanism. Living with ADHR: Challenges and Hope Living with a rare disease like ADHR is not easy. Many patients feel isolated because those around them do not understand why their bones hurt or why they tire easily. Moreover, the cost of modern treatments like burosumab can reach hundreds of thousands of ringgit per year. However, the good news is that awareness about ADHR is increasing. Now, there are genetic tests that can detect FGF23 mutations, and more specialized medical centers offer comprehensive treatment. If you or someone you know experiences mysterious bone pain, recurring tooth abscesses, or fractures without reason, do not ignore it. Seek advice from a doctor, especially a geneticist or rheumatologist. Remember, although ADHR is rare, there is a way out. With accurate diagnosis and appropriate treatment, patients can lead a more normal and pain-free life. Conclusion: ADHR may sound frightening – soft bones, constant pain, and tooth abscesses. But modern science and innovative treatments open a new chapter. From simple supplements to smart antibodies, we can now target the genetic cause of the disease. The most important thing is not to let fear prevent action. Get help, seek information, and remember – even if the FGF23 gene is damaged, our spirit does not have to be. --- Rujukan: Autosomal dominant hypophosphatemic rickets — Wikipedia https://en.wikipedia.org/wiki/Autosomal dominant hypophosphatemic rickets