Abstract #1412436: Nonclassical Presentation of Hypophosphatasia

Abstract

Hypophosphatasia (HPP) is a rare genetic disorder characterized by impaired mineralization (calcification of bones and teeth). The signs and symptoms of HPP vary widely and can appear from birth to adulthood. We report a case of delayed bone fracture healing in the setting of hypophosphatasia. A 48-year-old male patient with a past medical history of vitamin D deficiency was seen in the outpatient clinic for low ALP levels. He had delayed wound healing involving the left clavicular and multiple rib fractures after a motor vehicle accident that occurred in 2012, which ultimately needed multiple surgeries requiring 1.5 years to fully heal/fuse. This involved placing and removing multiple plates and screws as well as bone grafts. He denied other fractures, skeletal deformities, or dental problems. He does have normal development and does not have short stature. He has a history of vitamin D deficiency and is on vitamin D 2000 units daily. He was found to have a family history remarkable with two sons with low ALP and vitamin D beginning in childhood. The older son was noted to have lost his teeth early at age 3-4 years, with no history of fractures. Musculoskeletal examination: no swelling noted, and no tenderness was noted but the patient did have a bone spur on the elbow, knee, and heel. He is able to ambulate without assistance and was found to have no other skeletal deformity. Laboratory findings: ALP 31 U/L (Normal 34-122). Bone-specific alkaline phosphatase: 5.6 ug/L (Normal 6.5-20.1). Vitamin D 25 OH level: 84 (on replacement therapy). Calcium: 9.2 mg/dl, phosphorus 3.5 mg/dl, iPTH levels 23 pg/ml. DXA scan: shows T values on the lumbar spine of -1.8, right hip of -1.4, and right neck of -1.9, consistent with osteopenia. We checked vitamin B6 level: 1087.7 nmol/L, consistent with hypophosphatasia. The patient then underwent genetic testing and is positive for ALPL gene mutation (heterozygous). Both his 2 sons are positive for ALPL gene mutation. We present a case of hypophosphatasia with nonclassical presentations, his mild symptoms likely from incomplete penetration. HPP causes pathogenic variants in ALPL gene. This gene provides instruction for making an enzyme called tissue non-specific alkaline phosphatase (TNSALP) which plays an essential role in the mineralization of the skeleton and teeth. Mutation in the ALP gene leads to the production of an abnormal version of TNSALP that cannot participate effectively in the mineralization process. There is currently no cure for hypophosphatasia, however human recombinant enzyme replacement therapy called asfotase alfa is now available.