ODP629 A Case of Juvenile Onset Hypophosphatasia Diagnosed In An Elderly Patient With Recurrent Fractures.

Abstract

Background Hypophosphatasia (HPP) is a rare genetic disorder characterized by defective bone mineralization. Here we report a case of juvenile onset HPP in an elderly man. CASE A 77-year-old man presented for management of osteoporosis. He complained of joint pains and trouble walking. He had recurrent non-traumatic fractures since his teenage years and he and his sister were diagnosed with childhood rickets. He sustained fractures of both forearms, right ankle, right hip and left femoral neck, and had undergone right hip replacement and left femoral neck internal fixation. In his 20's, following a MVA he had several tooth extractions and eventually required dentures. He was misdiagnosed with osteogenesis imperfecta, vitamin D deficient osteomalacia and pseudogout, and had been treated with cholecalciferol and alendronate in the past. On exam, we noted a waddling gait, short stature and bowing of his knees. Labs revealed normal vitamin D 25-OH 48 ng/mL (30-100), and PTH 18 pg/mL (14-64), borderline corrected calcium 10.5 mg/dL (8.4-10.6) and elevated phosphorous 4.4 mg/dL (2.2-4.3). ALP was notably low 30 U/L (40-150) and had ranged between 15-46 U/L since 2009. These findings caught our attention and we ordered Vitamin B6 levels which were elevated >250. 0 ng/mL (2.1-21.7). Genetic testing identified two ALPL gene variants, a rare C.340G>A variant and a c.571G>A variant which has been found to be causative of HPP. His DXA scan showed normal L-spine (T-score 3.3) and significantly decreased BMD of the proximal 1/3 of the left forearm (T-score -4.4). Hip and femur were not assessed due to presence of hardware. He is scheduled to start treatment with Asfotase alfa. Conclusion HPP is caused by ALPL gene mutations, which lead to loss of function of the enzyme tissue nonspecific alkaline phosphatase (TSNALP). Clinical manifestations such as seizures, recurrent fractures and premature dental loss are observed. Pseudogout may occur due to intraarticular calcium pyrophosphate deposition, as in our patient. Characteristic lab findings are elevated metabolites of TNSALP, including urine inorganic pyrophosphate (PPi) and serum pyridoxal 5'phosphate (PLP) (biologically active metabolite of vitamin B-6). A persistently low ALP is most suggestive and may be a clue for early referral. Genetic testing is confirmatory, but novel mutations may be missed. Delayed diagnosis in our patient led to increased morbidity, potentially avoidable surgeries and inappropriate treatment with bisphosphonate which are contraindicated as they may increase risk for atypical fractures. Asfotase alfa is a TNSALP enzyme replacement therapy designed to address the underlying cause of HPP and studies show improvement in bone mineralization, fracture healing, decreased concentration of PLP and PPi, and improved physical function and quality of life. Cost and availability remain a barrier to many patients. Presentation: No date and time listed