GeneHealth - Your precision medicine

X-linked Hypophosphatemia

Disease Details

Family Health Simplified

Buy Membership

Description: X-linked hypophosphatemia is a genetic disorder characterized by low levels of phosphate in the blood due to impaired kidney phosphate reabsorption, leading to bone deformities and growth impairment.
Type: X-linked hypophosphatemia (XLH) is a genetic disorder. The mode of genetic transmission is X-linked dominant.
Signs And Symptoms: X-linked hypophosphatemia (XLH) is a genetic disorder characterized primarily by low levels of phosphate in the blood, leading to various symptoms:

**Signs and Symptoms:**
- **Rickets or osteomalacia:** Resulting in weakened bones and skeletal deformities, such as bowed legs.
- **Delayed growth:** Shorter stature compared to peers.
- **Dental problems:** Including abscesses and enamel defects.
- **Bone pain and joint stiffness:** Often impacting mobility and comfort.
- **Muscle weakness:** Potentially affecting physical activities.

Since you requested information on "nan," I might need clarification if you were referring to a specific medical term or context.

If you need more detailed information or have another question, feel free to ask!
Prognosis: X-linked hypophosphatemia (XLH) is a genetic disorder characterized by low levels of phosphate in the blood due to defective renal phosphate reabsorption.

**Prognosis:**
The prognosis for individuals with X-linked hypophosphatemia can vary. With appropriate management, including phosphate supplements and active vitamin D analogs like calcitriol, many patients can lead relatively normal lives. Regular monitoring and treatment adjustments are crucial to manage growth abnormalities, bone pain, and dental issues. Lifelong treatment is typically required, and some complications such as enthesopathy (inflammation where tendons and ligaments attach to bone) and osteoarthritis may develop over time. Early diagnosis and treatment often result in better outcomes.
Onset: X-linked hypophosphatemia (XLH) typically has an onset in early childhood, often between the ages of 1 and 2 years. The first signs may include bone deformities, such as bowed legs or knock knees, and delayed growth.
Prevalence: X-linked hypophosphatemia (XLH) is a rare genetic disorder with a prevalence estimated to be around 1 in 20,000 to 25,000 individuals.
Epidemiology: X-linked hypophosphatemia (XLH) is a rare genetic disorder with a prevalence estimated at 1 in 20,000 to 1 in 25,000 individuals. It is the most common form of hereditary rickets and is caused by mutations in the PHEX gene located on the X chromosome. This disorder is characterized by low levels of phosphate in the blood due to excessive loss of phosphate in the urine, leading to bone deformities and growth abnormalities.
Intractability: X-linked hypophosphatemia (XLH) is not considered entirely intractable, but it is a challenging condition to manage. It is a genetic disorder characterized by low levels of phosphate in the blood due to impaired kidney reabsorption of phosphate. Traditional treatments include phosphate supplements and active forms of vitamin D (such as calcitriol) to manage symptoms and improve bone health. Recently, burosumab, a monoclonal antibody targeting the fibroblast growth factor 23 (FGF23), has been approved for treating XLH, offering a more targeted therapy. While these treatments can significantly improve quality of life and symptoms, XLH remains a lifelong condition requiring ongoing management.
Disease Severity: X-linked hypophosphatemia (XLH) is a genetic disorder characterized by low levels of phosphate in the blood, leading to weakened bones. The severity of the disease can vary widely. Some individuals may experience mild symptoms such as dental abnormalities and minor bone pain, while others may suffer from severe symptoms like rickets in children, osteomalacia in adults, bone deformities, and significant growth retardation. If you need specific details on a particular aspect, please let me know.
Healthcare Professionals: Disease Ontology ID - DOID:0050445
Pathophysiology: X-linked hypophosphatemia (XLH) is a genetic disorder caused by mutations in the PHEX gene located on the X chromosome. This gene encodes a protein involved in the regulation of phosphate and bone metabolism. The mutations lead to excessive activity of fibroblast growth factor 23 (FGF23), which inhibits renal phosphate reabsorption and reduces the synthesis of vitamin D. Consequently, the condition is characterized by hypophosphatemia (low serum phosphate levels), leading to impaired bone mineralization and rickets or osteomalacia, depending on the age of onset.
Carrier Status: Carrier status for X-linked hypophosphatemia (XLH) typically applies to females. As XLH is an X-linked dominant disorder, females who carry one affected X chromosome can exhibit symptoms, though generally milder than affected males. Since males have only one X chromosome, if they inherit the affected X chromosome, they will express the disorder.
Mechanism: X-linked hypophosphatemia (XLH) is a genetic disorder characterized by low levels of phosphate in the blood, leading to rickets or osteomalacia. It is caused by mutations in the PHEX gene, which regulates phosphate metabolism.

### Mechanism:
In XLH, mutations in the PHEX gene impair its normal function in degrading fibroblast growth factor 23 (FGF23). Elevated levels of FGF23 reduce renal phosphate reabsorption and decrease the production of 1,25-dihydroxyvitamin D, leading to hypophosphatemia and defective bone mineralization.

### Molecular Mechanisms:
1. **PHEX Gene Mutations**: Mutations in the PHEX gene lead to the production of a dysfunctional PHEX protein.
2. **Increased FGF23 Levels**: The dysfunctional PHEX protein is unable to degrade FGF23 properly, resulting in elevated levels of this hormone.
3. **Phosphate Wasting**: High FGF23 levels lead to reduced expression of sodium-phosphate co-transporters in the renal tubules, causing phosphate wasting through urine.
4. **Impaired Vitamin D Metabolism**: Elevated FGF23 also inhibits the enzyme 1α-hydroxylase, reducing the conversion of 25-hydroxyvitamin D to its active form, 1,25-dihydroxyvitamin D, which is crucial for phosphate absorption in the gut.

These combined effects result in the clinical manifestations of XLH, including rickets, bone pain, and deformities.
Treatment: Conventional therapy consisted of medications including human growth hormone, calcitriol, and oral phosphate, and calcitriol; Unwanted effects of this therapy have included secondary hyperparathyroidism, nephrocalcinosis, kidney stones, and cardiovascular abnormalities.
In February 2018 the European Medicines Agency first licensed a monoclonal antibody directed against FGF23, the first drug targeting the underlying cause for this condition, called burosumab. It was then licensed by the US Food and Drug Administration in June 2018The leg deformity can be treated with Ilizarov frames and CAOS.
In the event of severe bowing, an osteotomy can be performed to correct the leg shape.
Compassionate Use Treatment: Compassionate use treatment for X-linked hypophosphatemia (XLH) often involves the use of medications that are not yet widely approved, but can be made available under certain circumstances. One example of such treatments is burosumab, an antibody that targets and inhibits fibroblast growth factor 23 (FGF23). Although burosumab is now FDA-approved, it was initially available under compassionate use programs before full approval.

Off-label or experimental treatments for XLH can include:

1. **Phosphate supplements and active vitamin D** (such as calcitriol or alfacalcidol): These are traditionally used to manage the condition by addressing phosphate dysregulation and bone issues.
2. **Growth hormone therapy**: This has been tried off-label in some cases to improve growth outcomes in children with XLH.
3. **Gene therapy**: Research is ongoing into potential gene therapy approaches to correct the underlying genetic defect.

Experimental treatments and clinical trials are continually evolving, so patients with XLH should consult with their healthcare provider about the most current and suitable treatment options.
Lifestyle Recommendations: Lifestyle recommendations for individuals with X-linked hypophosphatemia (XLH) include:

1. **Regular Monitoring**: Regular follow-ups with a healthcare provider to monitor phosphate levels and bone health.
2. **Balanced Diet**: Maintaining a healthy diet that includes foods rich in phosphate, though supplementation might still be necessary as advised by a doctor.
3. **Medication Adherence**: Strict adherence to prescribed medications, such as phosphate supplements and active vitamin D analogs.
4. **Physical Activity**: Engaging in weight-bearing exercises to strengthen bones, while avoiding high-impact activities that could increase the risk of fractures.
5. **Pain Management**: Using pain management strategies, which may include physical therapy, over-the-counter pain relievers, or other treatments prescribed by a healthcare provider.
6. **Dental Care**: Regular dental check-ups to manage dental abnormalities associated with XLH.
7. **Hydration**: Maintaining adequate hydration, as some treatments for XLH can affect kidney function.

It's important to develop a personalized care plan with a healthcare provider to address the specific needs related to XLH.
Medication: For X-linked hypophosphatemia (XLH), the commonly prescribed medications are phosphate supplements and active vitamin D analogs (such as calcitriol or alfacalcidol) to manage phosphate levels and promote bone health. Additionally, burosumab, a monoclonal antibody targeting FGF23, has been approved for treating XLH, offering a more targeted approach by directly addressing the underlying pathophysiology of the disease.
Repurposable Drugs: X-linked hypophosphatemia (XLH) is a genetic disorder that affects phosphate metabolism. A drug repurposed for the treatment of XLH is burosumab (Crysvita). Originally, treatments like phosphate supplements and active vitamin D analogs (e.g., calcitriol) were used to manage symptoms. Burosumab specifically targets and inhibits the activity of fibroblast growth factor 23 (FGF23), helping to regulate phosphate levels in the body more effectively.
Metabolites: X-linked hypophosphatemia (XLH) is primarily characterized by an imbalance in phosphate metabolism. The key metabolic feature of XLH is hypophosphatemia, which is a reduced level of phosphate in the blood. This condition stems from mutations in the PHEX gene, leading to increased levels of fibroblast growth factor 23 (FGF23). Elevated FGF23 reduces phosphate reabsorption in the kidneys and decreases the production of 1,25-dihydroxyvitamin D [1,25(OH)2D], the active form of vitamin D, which further impairs phosphate absorption from the gut. Consequently, the principal metabolites impacted in XLH are:
1. **Phosphate (inorganic phosphate, Pi):** Decreased blood levels.
2. **1,25-dihydroxyvitamin D [1,25(OH)2D]:** Reduced levels due to impaired conversion from its precursor forms.

Measurement of these metabolites can help in diagnosing and monitoring the treatment of X-linked hypophosphatemia.
Nutraceuticals: X-linked hypophosphatemia (XLH) is a genetic disorder that affects phosphate metabolism. Nutraceuticals for managing XLH primarily focus on phosphate and vitamin D supplementation to address hypophosphatemia and its effects. Common treatments include active forms of vitamin D such as calcitriol or alphacalcidol, along with oral phosphate supplements.

Research into nanotechnology for XLH treatment is still in early stages. Potential applications could involve targeted drug delivery systems to enhance the efficacy and reduce the side effects of current therapies. However, there are no established nanotechnology-based treatments for XLH at this time.

Always consult a healthcare professional for personalized medical advice.
Peptides: X-linked hypophosphatemia (XLH) is a genetic disorder characterized by low levels of phosphate in the blood due to the body's inability to properly regulate phosphate metabolism. This is often caused by mutations in the PHEX gene.

Regarding peptides: A notable peptide treatment for XLH is burosumab. Burosumab is a monoclonal antibody that targets and inhibits the activity of fibroblast growth factor 23 (FGF23), which is elevated in individuals with XLH and leads to increased phosphate loss.

Regarding nan (assuming you meant "nan," which might stand for "nanotechnology"): While nanotechnology is not a standard treatment for XLH, research is ongoing into various nanotechnology-based approaches for drug delivery and potentially for gene therapy applications that might benefit genetic disorders like XLH in the future. However, these are not yet standard treatments for the condition.