MON-366 X Linked Hypophosphatemic Rachitism: Case Report in Adult Patient

Abstract

BACKGROUND: X linked hypophosphatemia (XLH) is a rare genetic disorder, with an estimated prevalence of 1: 20,000 live births resulting from a mutation in the PHEX gene (phosphate regulatory endopeptidase), which causes increased levels of circulating fibroblast growth factor 23 (FGF23), reducing both renal reabsorption of phosphate and serum levels of 1,25-dihydroxyvitamin D3, causing chronic hypophosphatemia, rickets and osteomalacy. CLINICAL CASE: a 34 year old female with a height of 1.34 meters whose past medical history began at the age of three years old with a diagnosis of short stature, associated with genu varum and low serum phosphate levels. She received treatment with phosphate salts and calcitriol until eleven years old. During childhood, she underwent several surgical procedures to correct the genu varum. After stopping the treatment, she has presented four fractures in the lower extremities: bilateral femur, tibia and fibula that have required six surgical interventions (osteotomy, osteosynthesis and external fixation); the last surgery was performed in June of 2019; in addition, she has had multiple dental abscesses that required several oral surgeries. Current laboratory tests report: calcium 8.89 mg/dL (8.6-10), 24-hour urine calcium 72.17 mg (100-300) with urinary volume 1470 ml/24 h, serum creatinine 0.44 mg/dL (0.51-0.95), urine creatinine 43.72 mg/dL (29-226), serum phosphate 1.78 mg/dL (2.5-4.5), urine phosphate 17.75 mg/dL (40-136) PTH 86 pg/mL (15-65), alkaline phosphatase 134 ug/ dL (35-104), 25OH vitamin D 23 ng/mL (30-40). Tubular resorption of phosphate corrected for glomerular filtration rate (TmP/GFR:) 1.6 mg/dL (<2.8), Tubular Reabsorption of Phosphate (TRP) 89.96% (>80). Densitometry revealed a normal bone mineral density (BMD) in lumbar spine and hip. Radiographs of the lower limbs showed a difference of 19 mm of the right lower limb in anatomical length and 13 mm in functional length. A HLX genetic panel was performed, with a result of a definitely pathogenic Gene PHEX linked to chromosome X, with a pathological mutation 22 151 705 G> A p Trp456. The patient started treatment with calcitriol and dibasic phosphorus one month ago because of bone and muscle pain, stiffness, functional limitation, periodontal disease, recent hip fracture and indication of left hip replacement. She is candidate for burosumab (Anti-FGF23 Monoclonal Antibody) treatment.CONCLUSIONS: We present the case of adult patient with X-linked hypophosphatemia. Early treatment with phosphate is essential to avoid bone deformities. In adult patients, identifying pain, fractures or requirement of bone surgery, are indications for continuing treatment to improve quality of life, either with phosphate and calcitriol or with the new option, burosumab for pain control, improving functionality and stiffness.