X-Linked Hypophosphatemia Management in Adults: An International Working Group Clinical Practice Guideline.

Summary

An international, GRADE-based guideline for adult XLH recommends burosumab over no therapy for those with fractures/pseudofractures and suggests burosumab over conventional phosphate/active vitamin D in many scenarios. Diagnosis integrates clinical assessment with confirmation of renal phosphate wasting; PHEX variants are confirmatory but not required.

Key Findings

• Burosumab is strongly recommended over no therapy in adults with XLH and fractures/pseudofractures (GRADEd).
• Burosumab is suggested over conventional therapy even without fractures (conditional, GRADEd).
• Diagnosis relies on clinical assessment plus confirmation of renal phosphate wasting; PHEX variants confirm but are not mandatory.

Clinical Implications

Prefer burosumab in adults with XLH (especially with fractures/pseudofractures), implement multidisciplinary care, and use a structured diagnostic algorithm centered on renal phosphate wasting; use conventional therapy when burosumab is unavailable.

Limitations

• Evidence gaps necessitated Non-GRADED recommendations in some areas
• Limited head-to-head and long-term comparative data for adult outcomes and safety

Future Directions

Prospective registries and RCTs comparing burosumab vs conventional therapy, long-term outcomes (skeletal, renal, QoL), and cost-effectiveness analyses.