Endocrine Abstracts

Case: A 66-year-old female was referred to the Endocrinology clinic for suspected osteoporosis after a right femoral shaft fracture. As the site was atypical and the injury was low energy, a pathological fracture was suspected. There was a history of recurrent fractures sustained after the age of 30 years and were either spontaneous or from low-energy impacts (Table 1). Growing up, she was told that “there was something wrong with her bones” and required regular physiotherapy. She reported having a “funny” walk and the inability to run. She also described life-long myopathic symptoms. She could only walk for 10-15 yards with a stick before needing to rest. She took paracetamol and a buprenorphine patch for chronic pain and was on doxazosin and losartan for hypertension. She underwent a left hemiarthroplasty for NOF and an intramedullary nail to fix the right femoral shaft fracture. Her mother suffered recurrent fractures. Her grandson was diagnosed with a skeletal deformity in utero, which was deemed incompatible with life. Apart from a waddling gait, there were no clinical abnormalities. The relevant initial blood tests are listed in Table 2. Myeloma screen, tumour markers and creatine kinase were normal. Interestingly, the ALP was suppressed (chronically) with normal calcium and vitamin D and raised phosphate levels. DEXA scan was inconclusive due to spinal degeneration and metalwork in both hips. Congenital osteopathy was suspected, and a genetic screen revealed compound heterozygosity for pathogenic variants c.400_401delinsCA (p.Thr134His) and c.571G>A (p.Glu191Lys) in the HPP gene confirming Hypophosphatasia.

Outcome: Vitamin D and physiotherapy were commenced, and she was accepted for Asfotase alfa therapy in a specialist metabolic bone clinic.Learning points:• Hypophosphatasia results from mutation(s) in the tissue non-specific ALP encoding gene with reduced activity of ALP and defective mineralisation of bone and teeth.• Suspect hypophosphatasia in cases of recurrent fractures, myopathic symptoms, poor dentition, and suppressed ALP in the presence of normal calcium levels, especially if there is a family history of skeletal problems.