Hypophosphatemia refers to an abnormally low level of phosphate in the blood, an essential mineral that plays a critical role in energy production, muscle function, and nerve signaling, as well as in the formation of bones and teeth. This condition can arise from a variety of causes, including vitamin D deficiency, certain medication use, alcohol abuse, and medical conditions that interfere with phosphate absorption or increase its excretion. Symptoms of severe hypophosphatemia include muscle weakness, bone pain, and confusion, which can progress to serious complications such as heart and respiratory failure if left untreated.
About XLH
XLH, the most common form of genetic hypophosphatemia, is caused by pathogenic variants in the PHEX gene.1 XLH is an X-linked condition, meaning that the genetic variant (located on the X chromosome) only needs to exist in one copy of a patient’s genes to cause the condition. Women with XLH have a 50% chance of passing the condition to their children, regardless of gender, while men with XLH will pass it on to all their daughters and none of their sons.2
About TIO
TIO is a paraneoplastic condition of abnormal phosphorus and vitamin D metabolism caused by small, benign endocrine tumors that secrete the phosphaturic hormone, fibroblast growth factor 23 (FGF23), leading to impaired bone metabolism.3
Genetic testing plays a significant role in diagnosing and managing certain forms of hypophosphatemia, particularly those caused by genetic mutations that affect phosphate metabolism. Hypophosphatemia can arise from several inherited disorders, such as X-linked hypophosphatemia (XLH) and autosomal dominant hypophosphatemic rickets (ADHR), where mutations lead to improper handling of phosphate by the kidneys or impaired vitamin D metabolism. Additionally, genetic testing is important in cases of Tumor-Induced Osteomalacia (TIO), a rare disorder often associated with benign tumors that produce excess amounts of fibroblast growth factor 23 (FGF23), leading to phosphate wasting. Identifying the genetic mutations or the presence of these tumors through genetic and molecular testing can be crucial for appropriate management and treatment planning.
What is the Program?
Kyowa Kirin Inc. and Invitae have partnered to offer sponsored, no-charge genetic testing and counseling to patients being evaluated for a possible diagnosis of X-linked hypophosphatemia (XLH) or tumor-induced osteomalacia (TIO), are aged 6 months or older (for XLH) and 2 years or older (for TIO), reside in the United States or Canada, and meet certain other eligibility criteria.
An accurate diagnosis may impact the clinical management of the condition, including customizing care to a patient’s specific needs. The Kyowa Kirin Sponsored Hypophosphatemia Panel (13 genes) is designed to provide optimal diagnostic yield for patients with genetic forms of hypophosphatemia, based on the current scientific understanding. This panel also provides reasonable exclusionary yield for patients who are suspected of having TIO, in whom we would expect normal genetic test results.
The Kyowa Kirin Sponsored Hypophosphatemia Program is intended to improve patient safety and quality of care by shortening the time to an accurate diagnosis, facilitate prompt confirmatory testing, and help patients with XLH or TIO meet payor coverage requirements. Use of or participation in the Kyowa Kirin Sponsored Hypophosphatemia Program does not create any obligation to use, prescribe, or recommend any Kyowa Kirin products or services. No patient or health care provider may seek reimbursement for testing or counseling services provided under the Kyowa Kirin Sponsored Hypophosphatemia Program from any third party, including but not limited to, any government health care programs.
United States
Patients are eligible for this program if they are being evaluated for a possible diagnosis of X-linked hypophosphatemia (XLH) or tumor-induced osteomalacia (TIO), are aged 6 months or older (for XLH) and 2 years or older (for TIO), reside in the United States or Canada, and meet one of the following three criteria below:
Has documented hypophosphatemia and exhibits two or more of the following clinical signs and/or symptoms:
Canada
Patients are eligible for this program if they are being evaluated for a possible diagnosis of X-linked hypophosphatemia (XLH – 6 months or older) or tumor-induced osteomalacia (TIO – adult), reside in Canada, and meet one of the following criteria below.
Has documented hypophosphatemia and exhibits two or more of the following clinical signs and/or symptoms:
Or has a 1st or 2nd degree relative with a confirmed XLH diagnosis
Collect the patient’s sample using the specimen collection kit. Insert the completed TRF in the Invitae specimen collection kit and include it with sample shipment. You may also fax the order form to 415-276-4164.
Kyowa Kirin aims to discover novel medicines with life-changing value. As a Japan-based Global Specialty Pharmaceutical Company, we have invested in drug discovery and biotechnology innovation for more than 70 years and are currently working to engineer the next generation of antibodies and cell and gene therapies with the potential to help patients affected by a severe or rare disease. A shared commitment to our values, to sustainable growth, and to making people smile unites us across our four regions – Japan, Asia Pacific, North America, and EMEA/International. You can learn more about the business of Kyowa Kirin at www.kyowakirin.com.
CRYSVITA® (burosumab) is a recombinant fully human monoclonal IgG1 antibody developed by Kyowa Kirin. It is designed to treat X-linked hypophosphatemia (XLH) and fibroblast growth factor 23 (FGF23)–related hypophosphatemia in tumor-induced osteomalacia (TIO). CRYSVITA works by binding to and inhibiting the activity of FGF23, a hormone that reduces serum levels of phosphorus and active vitamin D. By blocking excess FGF23, CRYSVITA increases phosphate reabsorption in the kidneys and enhances the production of vitamin D, improving the absorption of phosphate and calcium in the intestines. This helps to correct hypophosphatemia and address bone mineralization defects associated with these conditions.
1. X-linked hypophosphatemia. Genetic and Rare Diseases Information Center (GARD) website. Updated 2018. Accessed January 3, 2019. https://rarediseases.info.nih.gov/diseases/12943/x-linked-hypophosphatemia.
2. Ruppe MD. X-linked hypophosphatemia. In: Adam MP, Ardinger HH, Pagon RA, et al, eds. GeneReviews. (Internet). Seattle (WA): University of Washington, Seattle; 1993-2019.
3. Dahir K, et al. Diagnosis and management of tumor-induced osteomalacia: perspectives from clinical experience. J Endocr Soc. 2021;5(9):bvab099.
