Introduction: Hypophosphatasia is a rare metabolic bone disease caused by one of several mutations in the ALPL gene which encodes tissue nonspecific alkaline phosphatase (ALP). It is usually diagnosed in childhood and can have a heterogenous clinical presentation depending on the extent of enzyme deficiency. Here we report the oldest known patient with hypophosphatasia.
Clinical Case: A 79-year-old woman with a history of medullary thyroid cancer (MTC) in remission, was referred to our metabolic bone disease clinic for the evaluation and treatment of osteopenia. She had suffered from numerous musculoskeletal complaints for several years and had received a diagnosis of polymyalgia rheumatica. However, her symptoms persisted despite a six month trial of prednisone. Although she had developed dental caries at a young age, she denied premature tooth loss. Her family history was significant for arthralgias and vertebral disc disorders in multiple family members, including both her children. Her mother carried a diagnosis of rheumatoid arthritis and osteoporosis. The only pertinent physical exam finding was short stature (Height -4’6”). A DEXA scan was performed using a Hologic unit and revealed a T Score of -1.0 at the L-spine and -1.9 at the femoral neck. A FRAX score predicted a 14% risk of major osteoporotic fracture and 4% risk of hip fracture.
Laboratory data revealed: Serum Calcium 9.3 (8.5-10.5 mg/dL), Albumin 4.3 (3.5-5.0 g/dL), ALP 21 (<130 U/L), Vitamin D 25OH 46.2 (>30 ng/ml), Intact PTH 28.3 (15.0-65.0 pg/ml), Vitamin B6 87.7 (2-21 ng/ml).
On review of her medical record, low ALP levels ranging between 20-30 U/L were noted to be present for the last twenty years. Given her history of musculoskeletal complaints, short stature, elevated Vitamin B6 and low ALP, genetic testing for hypophosphatasia was performed. Her results confirmed a known pathogenic mutation in the ALPL gene.
Conclusion: This case highlights the importance of reviewing ALP levels and relevant patient history to rule out hypophosphatasia prior to initiating therapy for osteoporosis. This condition is often unrecognized. Bisphosphonates, which are often the first line of treatment in osteoporosis, are contraindicated in hypophosphatasia as they can increase the risk of atypical fractures.1 Teriparatide may improve bone density depending on the extent of ALP deficiency. Asfotase alfa is a new agent that is currently available for the management of certain cases of hypophosphatasia.