MON-751 - An Atypical Biochemical Presentation of X-Linked Hypophosphatemia: A Case Report

Background:
X-linked hypophosphatemia (XLH) typically manifests in early childhood with symptoms of lower limb bowing, short stature, dental abnormalities, bone and joint pain, and fractures. Genetic mutations found in the PHEX gene underlie the typical biochemical features of XLH, including hypophosphatemia, elevated fibroblast growth factor 23 (FGF23), low to normal 1,25-dihydroxyvitamin D, elevated alkaline phosphatase, normal to elevated PTH, and normal urine calcium. We report a case of XLH that diverges from this typical biochemical profile.

Case Presentation:
A 38-year-old male with a prior history of osteoarthritis, fatigue, and lower extremity weakness presented for workup of XLH after learning of positive maternal family history. He had no history of clinical fractures but reported difficulty running during childhood and recurrent dental abscesses. He was treated for hypophosphatemia with phosphorus supplements and was told that he had hyperostosis type tissue. Surgery was recommended, which was deferred, and genetic testing was never performed. Physical exam revealed significant bowing of the legs without bony or spinal tenderness. Initial laboratory testing resulted in a serum phosphorus of 2.4 mg/dL (reference range 2.5-4.5 mg/dL), calcium of 9.3 mg/dL (reference range 8.6-10.3 mg/dL), intact parathyroid hormone of 97 pg/mL (reference range 16-77 pg/mL), alkaline phosphatase of 87 U/L (reference range 36-130 U/L), FGF23 of 113 RU/mL (reference range < 180 RU/mL), 1,25 (OH) vitamin D of 46 pg/mL (reference range 18-72 pg/mL), and 25(OH) vitamin D of 14 ng/mL (reference range 30-100 ng/mL). Urine calcium showed 83 mg calcium in 24h (reference range 55-300 mg/24h). Genetic testing revealed a hemizygous pathogenic PHEX gene mutation. The patient was initiated on vitamin D3 supplementation and is currently considering Burosumab therapy.

Discussion:
Although uncommon cases of this specific mutation have been documented, this specific case highlights a rare instance of XLH in which FGF23 and alkaline phosphatase are normal, diverging from the typical biochemical profile and pathophysiology of the disease. This case emphasizes the importance of genetic testing in diagnosing XLH when clinical suspicion is high, even in the presence of atypical laboratory results, guiding appropriate management and improving patient outcomes.

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