Abstract Introduction Hypophosphatasia is an uncommon disorder resulting from loss-of-function mutations in the ALPL gene, characterized by diminished alkaline phosphatase (ALP) levels and associated with dento-osseous and arthritic consequences. Clinical presentation may vary from life-threatening conditions to asymptomatic cases. Fractures, joint problems, calcifying polyarthritis may be observed. Here we present a case of hypophosphatasia found in late adulthood, characterized by two new mutations identified in the patient and her daughters. Clinical Case A 67-year-old female referred with a prolonged history of several fractures in femur and sacrum following the use of alendronate and denosumab throughout the post-menopausal phase, which began at 40 years old. She experienced the first fracture at 46 years old, right wrist fracture after falling from her height. 10 years ago she had femur fracture as a result of falling from height level and in same year she experienced pelvis fracture after falling on a soft surface. She had an ankle fracture during physiotherapy. She experienced multiple admissions to orthopedics and neurology clinics presenting with neuropathic complaints and immobilization due to pain. She received her last treatment for osteoporosis 4 years ago, single dose of denosumab, and since then, she has not undergone any treatment. She presented to the outpatient clinic in a wheelchair, had back pain and neuropathic symptoms. Her T score was -4.8 in L1-L4. Her calcium was 9.4 mg/dl, phosphorus was 4.04 mg/dl, parathyroid hormone was 26 ng/L, osteocalcin was 14.09 ng/ml, C-telopeptide was 0.46 ng/ml, and ALP was 48 U/L. She was initiated on a treatment regimen of teriparatide 20 mcg/day; however, during the treatment, her ALP levels were recorded at 30 U/L. Her previous ALP levels were reviewed from the file, revealing that they were low or at the lower limit. A mutation of ALPL c.917ATp(Asp306Val) heterozygote was detected which is defined as variant of uncertain significance. Teriparatide treatment was stopped. Her daughters were checked for ALP levels and was found to be 8 and 27 U/L. One of her daughters had the same mutation as heterozygote form and other daughter has ALPL (c.1078GA p.Gly360Arg) heterozygote mutation which is defined as pathogen according to clinVar genetic database. Considering both the identified mutation and the clinical presentation, a diagnosis of hypophosphatasia was considered, the patient was referred for enzyme replacement therapy. Conclusion Adult-onset hypophosphatasia is often underdiagnosed because of its variable presentation and may be misidentified as osteoporosis. Low ALP levels warrant further investigation. The use of bisphosphonates may result in atypical femoral fractures, making early diagnosis essential to prevent adverse outcomes. Asfotase alfa therapy has demonstrated considerable benefits, especially in pediatric cases, with emerging evidence supporting its efficacy in adult populations.Figure 1:femur fracture of patientx-ray findings after falling from her height level
Yazan et al. (Thu,) studied this question.