X-Linked Hypophosphatemia (XLH)
X-linked hypophosphatemia (XLH) is a rare genetic disorder characterized by abnormally low levels of phosphate in the blood, leading to impaired bone mineralization and skeletal abnormalities. Our company excels in the field of rare diseases, including XLH, offering a range of distinct advantages. We provide a comprehensive one-stop service for researchers and scientists dedicated to studying rare diseases.
Overview of XLH
XLH is inherited in an X-linked dominant pattern, meaning the mutated gene is located on the X chromosome. This condition, which primarily affects males but can also impact females, has a prevalence rate ranging from 1 in 20,000 to 1 in 60,000 individuals. XLH can present with various symptoms, including short stature, bowed or distorted legs, joint pain, dental abnormalities, and a tendency towards skeletal deformities like rickets or osteomalacia. Some individuals may also experience hearing loss or dental issues.
Fig.1 Manifestations of XLH. (Dahir, K., et al., 2020)Pathogenesis of XLH
The genetic basis of XLH lies in mutations within the phosphate-regulating endopeptidase homolog X-linked (PHEX) gene, located on the X chromosome. These mutations disrupt the normal regulation of phosphate metabolism, resulting in elevated levels of the phosphate-regulating hormone fibroblast growth factor 23 (FGF23). This dysregulation leads to excessive phosphate excretion through the kidneys and chronically low blood phosphate levels, culminating in significant musculoskeletal complications and growth abnormalities.
Fig.2 FGF23-mediated regulation of serum phosphorus. (Dahir, K., et al., 2020)
Diagnostics Development of XLH
Biochemical Tests
Blood tests are performed to measure phosphate levels, calcium levels, and markers of bone metabolism.
Typically, serum phosphate levels are low, while ALP levels are elevated. 
Other tests may include measuring
FGF23 levels and urinary phosphate excretion.
Genetic Analysis
Genetic testing involves analyzing the individual's DNA to identify mutations or deletions in the PHEX gene. Genetic analysis can be performed using various techniques such as Sanger sequencing, targeted gene panel testing, or next-generation sequencing.
Therapeutics Development of XLH
| Drug Names | Mechanism of Action | Targets | Research Phase |
|---|---|---|---|
| Alfacalcidol | Help the phosphate levels normalize | Vitamin D receptor | Approved |
| Calcitriol | Counteract the downstream effects of excess FGF23 | Vitamin D receptor | Approved |
| Burosumab | The monoclonal antibodies against FGF23 | FGF23 | Approved |
| Cinacalcet | Control secondary and tertiary hyperparathyroidism in XLH | CaSR | Clinical research |
| Thiazide diuretics | Reduce hypercalciuria | NCC | Clinical research |
| Anastrozole | Stabilize bone age and minimize height impairment | Aromatase | Clinical research |
Our Services
We have a team of highly skilled professionals with extensive knowledge in the field, including geneticists and laboratory experts, who collaborate to deliver exceptional results. With our animal models and therapeutic development platform, we provide support at every stage of your projects.
Therapeutics Development Platforms
Animal Models of XLH
Animal models have been valuable tools for investigating underlying mechanisms and exploring potential therapeutic strategies. Our company provides various animal models of XLH to mimic certain aspects of the disease and provide insights into its pathogenesis and potential therapeutic interventions.
One notable animal model of XLH is the Hyp mouse, which derives from a spontaneous mutation in the PHEX gene, mirroring the genetic defect and exhibiting many of the characteristic features of human XLH.
Optional Models:
- Hyp mice model, etc.
The advancements in genetic engineering techniques, such as CRISPR/Cas9 technology, it may be possible to introduce specific mutations or genetic modifications to mimic XLH-related pathologies more accurately.
Optional Models:
- Ska1 model; Jrt model, etc.
Why Choose Us
With our expertise and specialized knowledge, we offer a range of services encompassing pharmacokinetic studies and drug safety evaluation. By offering a holistic approach and an integrated platform for rare disease research, we aim to facilitate breakthroughs, advance scientific understanding, and ultimately contribute to the development of innovative therapies.
If you are interested in learning more about our services and how we can support your research endeavors, please do not hesitate to reach out to us for further information.
References
- Dahir, Kathryn et al. "X-Linked Hypophosphatemia: A New Era in Management." Journal of the Endocrine Society 4.12 (2020): bvaa151.
- Beck-Nielsen, Signe Sparre et al. "FGF23 and its role in X-linked hypophosphatemia-related morbidity." Orphanet journal of rare diseases 14.1 (2019): 58.
All of our services and products are intended for preclinical research use only and cannot be used to diagnose, treat or manage patients.