Endocrine Abstracts

JOINT2164

Introduction: X-linked hypophosphatemic rickets (XLH) is caused by variants in the PHEX gene, leading to hypophosphatemia and significantly elevated FGF23 levels. However, there is limited data in the literature regarding reference values for FGF23 in healthy paediatric subjects and cut-off in patients with XLH.

Case report: We present the case of a 3-year-old female patient referred to our clinic for an abnormal gait, characterized by clumsy running and frequent falls. Blood tests showed normal calcium and magnesium levels, severe hypophosphatemia, elevated alkaline phosphatase and bone isoenzyme levels, normal parathormone levels, normocalciuria, and increased level of urinary phosphate. FGF23 levels were within the reference range at 24. 2 pg/mL (reference range: 23. 2–95. 4 pg/mL). X-rays revealed lateral bowing of the femurs and tibias, predominantly tibial varus deformity, widened metaphyses of the tibia and femur, irregular physeal contours, medial sclerosis, and bilateral femoral neck varus. Initial diagnosis of inherited non-FGF23-mediated hypophosphatemic rickets was made. Calcitriol and inorganic phosphate salts treatment was started. During follow-up, FGF23 levels progressively increased (44. 6 pg/ml at 3 months and 80. 6 pg/ml at 6 months). Alkaline phosphatase remained elevated while phosphate levels were low (2. 8 mg/dl at 6 months). Other blood tests showed no significant changes. Based on these clinical and laboratory findings, a genetic evaluation was performed. Genetic analysis identified the c. 1601C>T, p. Pro534Leu heterozygous variant in the PHEX gene, classified as pathogenic and associated with XLH.

Conclusions: Generally, FGF23 levels appear significantly elevated in patients with XLH, but they can sometimes appear falsely normal. Moreover, reference values for the paediatric age group have not yet been standardized: FGF23 levels exhibit diurnal fluctuations and vary based on age, pubertal stage, and clinical context, as demonstrated in a 2024 Italian monocentric study (Baroncelli et al. ). Multicentric studies are needed to establish FGF23 reference values for paediatric patients and those with XLH genetically confirmed. In clinically and radiologically suspicious cases for XLH, without definitive laboratory tests, paediatric endocrinologists should frequently reassess the complete calcium-phosphorus profile, including FGF23 and urinary tests, while also considering genetic evaluation even when FGF23 levels continue to appear normal. A change in the diagnostic suspicion, awaiting the results of genetic investigation, and the early start of specific PHEX’s treatment could improve the patient’s clinical outcome.