SAT-LB085 First Report of Burosumab (Anti-FGF23 Monoclonal Antibody) for Rickets Complicating HRAS-Associated Cutaneous Skeletal Hypophosphatemia Syndrome

Background: Cutaneous skeletal hypophosphatemia syndrome (CSHS) is caused by somatic mosaicism of a RAS family gene (ie. HRAS, NRAS, KRAS). CSHS features: 1) congenital epidermal, melanocytic, or sebaceous nevi, 2) elevated circulating FGF23 levels that cause renal phosphate wasting and skeletal hypomineralization, and 3) focal bone lesions ipsilateral to the nevi as a possible source of excess FGF23. Conventional therapy for rickets in CSHS (phosphate salts and bioactive vitamin D) mirrors treatment for X-linked hypophosphatemia (XLH) with elevated circulating FGF23. Current therapy aims to treat signs and symptoms rather than the etiology. Clinical Case: A 21-month-old boy with left, widespread, unilateral nevus sebaceous developed bilateral lower extremity bowing with a wide-based gait. His serum phosphorus level was low at 2.1 mg/dl (Nl: 3-6) and FGF23 was elevated at 279 RU/mL (Nl: < 230). We prescribed conventional therapy for hypophosphatemic rickets and diagnosed linear sebaceous nevus syndrome, confirmed by mutation analysis of affected skin harboring HRAS p.Q61R (c.182A>G). Adherence to medical therapy was problematic, and he sustained 3 major long-bone fractures. By age 6 years, a walker was required to ambulate short distances with mostly wheelchair-dependence from pain and muscle weakness. Based on his elevated FGF23 level and clinical decline, burosumab (anti-FGF23 fully human monoclonal antibody), FDA-approved in 2018 for XLH, was initiated off-label. After weaning conventional therapy, burosumab was administered subcutaneously as a single dose of 0.8 mg/kg (20 mg) and decreased to 0.3 mg/kg (6 mg) two weeks later. Burosumab was then given every 2 weeks and adjusted by 0.1 mg/kg to maintain fasting serum phosphorus in the low-normal range for age (3.5 - 4.5 mg/dL). Laboratory and clinic follow-up occurred just prior to each injection for 3 months until serum phosphorus was stable as he received approximately 0.4 mg/kg (8 mg per dose). Biochemical testing and clinic visits will occur monthly for 3 months and are planned for quarterly afterwards, with repeat radiological imaging every 3-6 months for the first year of therapy. Duration of burosumab treatment has been 5 months. After his initial burosumab dose, serum phosphorus increased from 1.7 to 3.7 mg/dL and remained normal [Nl: 3.0 - 6.0 mg/dL] thereafter. Radiographs of his wrists and knees 3 months into therapy revealed striking improvement of his rickets but persisting focal bone lesions, characteristic of CSHS, on the left side. He now walks independently with endurance, strength, and resolving pain. Quality-of-life is markedly improved. Burosumab treatment is being tolerated well without side effects. Conclusion: Burosumab seems to be an effective therapy for FGF23-mediated rickets in pediatric CSHS. Unless otherwise noted, all abstracts presented at ENDO are embargoed until the date and time of presentation. For oral presentations, the abstracts are embargoed until the session begins. Abstracts presented at a news conference are embargoed until the date and time of the news conference. The Endocrine Society reserves the right to lift the embargo on specific abstracts that are selected for promotion prior to or during ENDO.