Center for X-Linked Hypophosphatemia

The Yale Center for X-Linked Hypophosphatemia and Related Conditions (YC-XLH) was established in 2006 as an NIH/NIAMSD-sponsored Center of Research Translation to support research, clinical trials, and clinical care in the field of endocrinology. As a dynamic research site, we are constantly investigating new and more effective treatments for a host of rare diseases including, but not limited to, X-linked hypophosphatemia, osteogenesis imperfecta, tumor-induced osteomalacia, hypoparathyroidism and hypocalcemia.

YC-XLH is dedicated to advancing the health of patients and study participants with disorders of phosphate metabolism and other related skeletal conditions by:

• Conducting ongoing research of XLH and related conditions
• Developing new therapies to improve long-term outcomes
• Providing expert care and management to those affected by these disorders
• Serving as an educational and referral resource for both physician and patient communities

Interest in XLH and phosphate metabolism has been evident at Yale for many years. Dr. Howard Rasmussen planted the local seeds of interest in XLH in the 1970s, caring for many patients and performing early therapeutic trials in collaboration with Dr. Constantine Anast in Boston. Training with Drs. Rasmussen and Anast, Drs. Karl Insogna and Thomas Carpenter established a coordinated approach to both clinical research and family-centered care in the 1980s. The program's subsequent growth led to the development of a regional and national care and research center, with the formal establishment of the YC-XLH in the early 2000s. From then through the present, YC-XLH has been influential in underlying research leading to novel therapies for XLH, enhancing our understanding of the pathophysiology, and advocating for the well-being of affected patients.

• Described aberrant parathyroid hormone (PTH) secretion in XLH and identification of therapies to address this abnormality
• Characterized mineralizing enthesopathy in humans with XLH and in Hyp mice
• Described the beneficial effects of conventional XLH therapy on dentition, but no impact upon enthesopathy in XLH
• Led first-in-man studies using anti-FGF23 antibody therapy in XLH, with leading roles in multi-dose trials in XLH, Tumor-Induced Osteomalacia, and Cutaneous Skeletal Hypophosphatemia Syndrome
• Described skeletal histologic and histomorphometric response to long term therapy with calcitriol and phosphate in XLH
• Explored the role of muscle function and ATP flux in response to therapy of hypophosphatemic disorders
• Identification of FGF7 as a novel phosphatonin
• Described population growth curve data for children with XLH
• Described effects of calcitonin on FGF23 secretion
• Identified hypophosphatemia as a complication of specialized formula use in at-risk patients, leading to reformulation of the product