Endocrine Abstracts

JOINT3977

Introduction: XLH is a rare, genetic, chronic, progressive, lifelong musculoskeletal disorder characterised by renal phosphate wasting caused by excess FGF23 activity. It has biological and clinical consequences since early childhood: hypophosphatemia, low active vitamin D, craniosynostosis, rickets, bone deformity, short stature, and nephrolithiasis. The inheritance pattern of XLH is X-linked dominant, and the total incidence of XLH (paediatrics and adults) is 1 in 20, 000. There are two main therapeutic options: conventional therapy (phosphate supplements and active vitamin D) and biological therapy (Burosumab, a specific antibody against FGF23, EMA approved since 2018).

Subjects and Methods: Between 2018 and 2024, 13 children (7 girls) (median age = 4. 1 years, 1. 8-6. 8 years) and 1 adolescent girl were diagnosed and treated for XLH in a tertiary centre of pediatric endocrinology. Clinical, biological and radiological parameters were measured every 3-6 months: height, bone deformity, cranial circumference, 6MWT, serum calcium, phosphate and alkaline phosphatase, serum 25 OHvitamin D, PTH, TRPh, rickets severity score (RSS) and mechanical and anatomical axis of the lower legs.

Results: The children were first treated with conventional therapy and then switched to biological treatment after a median time of 4. 2 years. The main reasons for therapeutic alternatives were unimproved short stature and low leg deformity needing orthopaedic correction. None of the children on conventional therapy developed nephrolithiasis. After a median time of 2. 3 years (0. 5-3. 5 years), Burosumab treatment (median dose 1 mg/kg) showed a clear improvement of the clinical, biological and radiological data: an average 0. 425 SDS at week 96 improvement of Z-score for height, a constant increase of serum phosphorus to low normal levels, a constant decrease of alkaline phosphatase. Minor local reactions at injection sites or flu-like symptoms were described in the first doses but without clinical significance. None of the children needed orthopaedic correction. None of the children developed hyperparathyroidism.

Conclusions: Although a rare disease, XLH can be easily identified, evaluated, and treated by multidisciplinary teams from specialised bone disorders children’s centers.