X-Linked Hypophosphatemia (XLH)
X linked Hypophosphatemia (XLH) is a kind rare genetic condition where there are extremely low phosphate levels in the blood resulting in poor bone mineralization and skeletal deformities. We are the market leaders in rare diseases, including XLH, which allows us to gather a lot of benefits. We offer an unmatched service to researchers and academics working in rare diseases.
Overview of XLH
XLH is passed down through the X chromosome from affected parents. It is mostly a male disease but may affect females as well. The prevalence of XLH is between 1 in 20,000 and 1 in 60,000 people. XLH has several symptoms including but not limited to short stature, bowlegged or distorted legs, skeletal and joint pain, poor dental health, along with skeletal deformities such as rickets or osteomalacia. In some cases, patients may also suffer from hearing problems or teeth problems.
Fig.1 Manifestations of XLH. (Dahir, K., et al., 2020)Pathogenesis of XLH
X-linked Hypophosphatemia occurs because of mutations in the PHEX gene, which is found on the X chromosome. These mutations alter phosphate balancing processes and increase the levels of phosphate-regulating hormone fibroblast growth factor 23 (FGF23). Dysregulation of governing factors also results in excessive kidney phosphate wasting and low serum phosphate levels, leading to severe muscles and bones abnormal changes and growth deficits.
Fig.2 FGF23-mediated regulation of serum phosphorus. (Dahir, K., et al., 2020)
Diagnostics Development of XLH
Biochemical Tests
Phosphate, calcium and other bone turnover markers are obtained and endpoints are determined. Serum phosphate levels are typically subnormal while ALP levels are elevated. 
Biochemical TestsFGF23 level and urinary phosphate excretion are measured.
Genetic Analysis
Testing of Ionizing Radiation Sensitive Cells, also called known as TRIS, refers to studying provided biological materials in order to detect any mutations or chromosomal deletions of the PHEX genes. Genetic studies can be undertaken using 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
A complete suite of advanced services is provided, particularly therapeutic development at every level, through animal models and a geneticists included laboratory department-led structural unit. Our skilled professionals have relevant experience in the area alongside geneticists and laboratory professionals, all of whom work together to achieve the best results.
Therapeutics Development Platforms
Animal Models of XLH
For the investigation of underlying mechanisms and the possible treatment approaches animal models have served as invaluable tools. Our company will provide several animal models of XLH to simulate certain disease aspects and advance understanding of its pathogenesis and therapeutic possibilities.
Hyp mouse is one unique example of an animal model of XLH. This model mouse suffers from XLH because of a single spontaneous mutation in PHEX gene which completely recapitulates the genetic defect and many of the clinical features of XLH.
Optional Models:
- Hyp mice model, etc.
With the recent progress in genetic engineering it may now be realistic to attempt to introduce some specific mutations or genetic alterations in order to more accurately create different XLH pathologies.
Optional Models:
- Ska1 model; Jrt model, etc.
Why Choose Us
We have focused on providing services for pharmacokinetic studies and drug safety evaluation as opposed to other research activities. By providing an all-in-one approach for primary and rare disease investigations, we aim to facilitate scientific breakthroughs and the understanding of the disease's mechanisms in order to enhance the development of new cures.
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.