2009 Southern Regional Meeting Abstracts

Case Report: Case summary
We describe here a 39 year old white female with childhood rickets and persistent and refractory hypophosphatemia since her adolescence. Investigations including genetic analysis confirmed X-linked hypophosphatemia (XLH) The patient had multiple sequelae, including chronic pain, recurrent headache, and musculoskeletal malformations like short stature, bowed legs and spinal stenosis requiring spinal surgery. She was treated with oral phosphate supplements and calcitriol, which improved her biochemical parameters, as well as symptomatic treatment for chronic pain. In the last 5 years, the serum calcium ranged from 8.0-9.8 mg/dl, phosphorous 1.5-3.2 mg/dl, creatinine 0.5-0.7mg/dl and iPTH 29-40 iu. Of interest is the fact that an investigation of recurrent headaches by MRI led recently to the diagnosis of Chiari malformation.
Discussion
XLH has an incidence of 1 in 20,000. These patients have abnormal phosphaturia leading to phosphorus depletion and musculoskeletal derangements in childhood (rickets) and adulthood (osteomalacia). Despite severe bone malformations and late diagnosis of the disease, our patient maintained normal renal function with no evidence of hyperparathyroidism and enjoyed a relatively good quality of life. The association of XLH with Chiari malformation is extremely rare (only 2 published reports so far). Recent investigations in the pathophysiology of this disease suggest that PHEX gene may cause an aberrant PHEX protein. Its substrate, while not yet identified, has been named phosphatonin. Phosphatonin FGF23 may be the one of the substrates and has been reported to be elevated in XLH patients. FGF-23 may reduce Na-dependent Pi transport in the kidney and induces phosphaturia. Studies suggest that the combination of 1,25(OH), D, and 24,25(0H), D, may be superior to either agent alone in the restoration of normal mineralization in XLH.
Conclusion
X-linked hypophosphatemia is a relatively rare disorder with severe musculoskeletal malformations. The association with recurrent headaches warrants a screening for Chiari malformation, in this population since the diagnosis may often be missed. Also, the recent discovery of PHEX gene and FGF-23 as a possible factor in renal phosphate wasting opens the doors for potential new treatment options.