A Novel PHEX Mutation in A Case Followed Up with A Diagnosis of X-linked Hypophosphatemic Rickets

Introduction: X-linked hypophosphatemic is a result of a mutation which leads to loss of function in the phosphate-regulating endopeptidase homolog X-linked (PHEX) gene. The case is here presented of a patient followed up for XLH rickets, with the formation of a stop code through frame-shifting mutation in the PHEX gene. Case Report: An 18-month old male infant presented at our clinic with the complaint of curvature in the legs. In the physical examination of the infant, height was measured as 78 cm (-1.67 SDS) and weight was 12.5 kg (0.52 SDS). Deformity was present in the frontal protusion, the wrist widths and the legs. Laboratory test results were determined as phosphorus: 2.3 mg/dL (n=3.5-4.7), calcium: 9.8 mg/dL (n=8.5-10.5), alkaline phosphatase (ALP) 707 IU/L (n=40-150), 25(OH) D vitamin:18 mu g/L (n=18-40), PTH: 79 pg/mL (n=15-68), and tubular phosphorus reabsorption was low (71%). Visualisation on wrist radiographs of collapse in the metaphyseal sections of the radus and ulna and metaphyseal irregularity. Conventional treatment was started. Next generation sequence analysis of the proband revealed the presence of a hemizygous c.281_288delTTCCCGAA (p.lle94ArgfsTER14) frameshift variant in PHEX gene. This novel variant is pathogenic according to the ACMG criteria, and not reported in any database before. While full-fill clinical recovery was not achieved with conventional treatment and some complications occured, Burosumab treatment was started. Conclusion: Here presented of a patient who was diagnosed with XLH, and was then determined with a novel mutation in the PHEX gene. The current treatment options directed at the basic pathology render genetic diagnosis more important in cases of hypophosphatemic rickets.