Endocrine Abstracts

Background: X-linked hypophosphataemia (XLH) is a rare genetic disorder due to inactivating PHEX mutations, leading to elevated FGF23, renal phosphate wasting, and decreased 1,25 dihydroxy-vitamin D levels. Conventional therapy for XLH consists of activated vitamin D and oral phosphate replacement, but this is often poorly tolerated. Burosumab is a recombinant human monoclonal antibody against FGF23 and unlike conventional therapy, targets the underlying pathophysiology of XLH.

Methods: A retrospective audit was carried out on five adult patients (>18 years) attending the Queen Elizabeth University Hospital in Glasgow with a diagnosis of XLH and confirmed PHEX mutations who are receiving subcutaneous Burosumab every 4 weeks. Activated vitamin D and oral phosphate were discontinued 7 days prior to initiation of Burosumab therapy.

Results: All patients had a history of lower limb deformities and previous orthopaedic interventions. Four patients experienced recurrent dental abscesses, four had previous fractures/pseudofractures and one had a Chiari malformation. The median age at Burosumab initiation was 37 years (IQR 20–39), with a median dose of 80 mg (IQR 70–90). The median height was 148.5 cm (IQR 140.5–157.0), and the median BMI was 32 (IQR 27.2–39.4). The median treatment duration was 272 days (IQR 263–348). Prior to Burosumab initiation, all patients had low serum phosphate levels (median 0.65 mmol/l, IQR 0.55–0.68). Serum phosphate normalised in all patients within 4 weeks of treatment, with sustained levels observed at 12 weeks (median 0.96 mmol/l, IQR 0.9–1.0).

Conclusions: Burosumab appears well tolerated and effectively normalises serum phosphate levels in adults with XLH. However, further data is required to understand the impact of this treatment on the long-term complications of XLH.