MON-497 Adult Onset Hypophosphatasia: Before and After Treatment with Asfotase Alfa

Abstract

Hypophosphatasia is a rare inherited bone disease resulting from mutations in the gene encoding tissue-nonspecific alkaline phosphatase (TNSALP), an enzyme predominant in skeleton, liver, kidney and teeth. Diminished TNSALP activity causes accumulation of substrates that inhibit bone mineralization resulting in debilitating pain, fractures and low alkaline phosphatase (ALP) levels. In 2015 the FDA approved asfotase alfa, a bone-targeted recombinant TNSALP used for enzyme replacement therapy. We present a case of hypophosphatasia treated with asfotase alfa resulting in improvements in whole body scan and pedometer step counts. In 2014, a 52-year-old female with chronic pain presented with over 30 years of bony pain, poor balance, falls, fractures and life-long dental disease. Physical exam displayed tenderness of long bones and waddling gait. Blood work was remarkable for low ALP at 11 U/L (normal 35-120 U/L) and low bone-specific ALP of 3 ug/L (normal 7.0-22.4 ug/L). Vitamin B6 level was >2000 nmol/L (normal 20.0-125.0 nmol/L). Calcium level was 9.8 mg/dL (normal 8.5-10.1 mg/dL). Serum phosphorus was elevated at 5.2 mg/dL (normal 2.3-4.6 mg/dL). Intact parathyroid hormone level was elevated at 114.1 pg/mL (normal 18.5-88.0 pg/mL), with known diagnosis of chronic kidney disease, GFR 27 mL/min. Her 24-hour urine calcium, serum protein electrophoresis, celiac test, thyroid studies and vitamin D level were normal. N-telopeptide was elevated at 25.9 nM (normal 6.2 to 19.0 nM). SPECT whole body scan demonstrated increased uptake with multiple fractures of the axial skeleton and proximal femurs; consistent with oncogenic osteomalacia. Fibroblast growth factor 23 and indium 111 octreotide scan showed no evidence of malignancy. DEXA scan showed osteopenia of the hip and forearm. She was diagnosed with adult-onset hypophosphatasia. Initially, due to lack of options, she was treated with denosumab. After three injections, she developed a new atypical femur fracture requiring surgical rod placement; denosumab was discontinued. In 2017, she was started on asfotase alfa with significant improvements in balance, endurance, and bone pain. Prior to treatment, the patient required narcotic oral pain medicine, fentanyl patch and an assistive device to walk 3000 steps daily; after treatment, she is walking over 10,000 steps daily without any pain pharmacotherapy. Repeat whole body scan showed less focal uptake overall, consistent with healing fractures. This case highlights clinical proof of improvement after treatment with asfotase alfa based on increased daily step count and healing fractures on whole body scans. Asfotase alfa is a newly approved therapy for hypophosphatasia and therefore long-term outcomes are not yet available, however short term patient reported subjective findings and clinical data are reassuring for successful treatment.