Endocrine Abstracts

JOINT2162

Introduction: Phosphopenic rickets (FPR) is a group of disorders characterized by renal phosphate loss due to hereditary or acquired causes, leading to impaired bone mineralization. It affects both children and adults. This study presents the clinical data of patients diagnosed with FPR from a single center.

Patients and Methods: We present the clinical and genetic characteristics of pediatric (index) patients evaluated for hypophosphatemia and their subsequently diagnosed relatives between 2004 and 2024.

Results: A total of 33 cases (M:F = 21:12) from 26 families were identified. The median (range) age at diagnosis was 3. 9 (0. 6–31) years, serum phosphate (sP) was 2. 6(0. 5–3. 8) mg/dL, and the mean±SD TmP/GFR 1. 7±0. 9 mg/dL. Sixteen (48. 5%) had fibroblast-growth-factor-23 (FGF23)-dependent hypophosphatemic rickets (HPR) (14 hereditary, 2 acquired – both infants with liver failure), 10 (30%) from 8 families had vitamin D-dependent-rickets-(VDDR) [type 1 (n = 8)/type 2 (n = 2)], and 7(21%) had FGF23-independent-renal-tubular-dysfunction (RTD). In hereditary HPR, the age at diagnosis was 4. 8 (2-31) years, follow-up 14. 1(6. 6-21. 8) years. All patients had short stature, genu varum, and/or dental abnormalities. The Thacher score was 6. 1(5–8). While 4(28%) had enthesopathy, nephrocalcinosis was detected in 2(14%). Eight(57%) had corrective surgery, 2(%14) had history of fractures. Two(14%) were treatment naive while 6(42%) discontinued in adulthood. PHEX variant was identified in 4(28%). One was started on burosumab aged 10 years, resulting in significant improvement in genu varum. In VDDR age at diagnosis was 1. 6(1. 3-4) years. Nine(90%) presented with delayed walking and 9 had consanguineous parents. Wrist widening was observed in all, while genu varum was present in 7(70%). Height SDS at presentation was -2. 0(-0. 5/-4. 5) and sP 2. 9 mg/dL(1. 7-3. 3). In type 1 VDDR, CYP27B1 variant was found in 6/8 (homozygous n = 5; compound heterozygous n = 1) while in type 2 VDDR a homozygous pathogenic variant in VDR was found in one. In RTD, age at diagnosis was 7(3-14. 3) years, height SDS -3. 5(-0. 6/-4. 3), sP 2. 6 mg/dL(0. 5-2. 9), and TmP/GFR 1. 7(0. 2-2. 5)mg/dL. Diagnosis included cisplatin toxicity (CT)(n = 1, Pearson syndrome n = 1, cystinosis n = 2, and RTD n = 3. All but one (CT) had skeletal anomalies. In one with RTD, a pathogenic variant in the SLC34A3 gene was identified.

Conclusion: These results highlight the wide range of clinical and genetic characteristics of patients with hypophosphatemia. Elucidation of etiology will enable early and correct diagnosis but delay causes severe morbidity. Burosumab, an FGF23 inhibitor, targeted therapy for X-linked hypophosphatemia improves skeletal deformities and growth in children, enhances fracture healing, reduces pain, and boosts physical activity in adults.