THU458 Demineralization Zebras: A Rare Case Of Hypophosphatasia In An Adult Presenting With Osteopenia

Abstract

Abstract Disclosure: B.P. Ramchandani: None. A. Khan: None. H. Aftab: None. Introduction: Hypophosphatasia (HPP) is a rare genetic bone disease with only 500-600 cases reported in the United States. It is characterized by mutations in the tissue non-specific alkaline phosphatase (TNSALP) gene, leading to impaired bone mineralization. HPP presenting in the perinatal period is fatal. During infancy, rachitic deformities develop by age 6 months. Children present with early loss of deciduous teeth and delayed milestones while in adulthood, HPP is characterized by recurrent fractures, osteoporosis, and muscle weakness. We describe a case of HPP diagnosed in a patient after low ALP was discovered on laboratory testing. Case: A 69-year-old female presented for the evaluation of osteopenia. She had a history of fracture of the right knee as well as fracture of the base of the right 5th metatarsal and lateral aspect cuboid, which healed well with conservative management. Dental history was significant for 5 implants over the last 15 years. She was on vitamin D supplements and had also taken risedronate for osteopenia for 14 years which was discontinued at her first visit with us. Family history was significant for osteoporosis in her mother. Initial lab studies were significant for an ALP of 29 U/L (ref range 39-113 U/L), phosphate of 4.9 mg/d (ref range 2.4-4.8 mg/dl), pyridoxal 5’-phosphate level (vitamin B6) of 308 nmol/L (ref range 20-125 nmol/l), a vitamin D 25-OH level of 20 ng/mL (ref range >30 ng/ml) and PTH of 49 pg/dl (ref range 15-88 pg/ml). Repeat lab testing done 6 months after stopping risedronate showed consistent similar results with an ALP of 32 U/L, phosphate level of 5.1 mg/dl, vitamin B6 level of 349 nmol/L, and vitamin D 25OH level of 26 ng/mL. Bone density scan revealed a lumbar spine BMD of 1.503 g/cm2 (T-score 2.5) and a mean total hip BMD of -0.3 consistent with osteoporosis of spine and osteopenia of hip. Genetic testing and counseling were offered to the patient, however she declined. Discussion: Our patient presented with recurrent fractures and loss of dentition requiring multiple dental implants in the background of osteopenia. Given persistently low serum ALP and elevated serum vitamin B6 levels her presentation suggested a diagnosis of HPP. Management includes supportive treatment with prompt treatment of fractures, and routine dental care. Although there is no approved medication for adults, enzyme therapy replacement with asfotase-alfa (a recombinant human ALP) is FDA-approved for pediatric-onset HPP which improves bone mineralization and muscle strength, however discontinuation of therapy leads to reappearance of bone hypomineralization. Once the diagnosis is made, genetic testing and counseling should be offered to prevent complications in future pregnancies. Presentation: Thursday, June 15, 2023