Category: Calcium/Bone Disorders
Objective : Juvenile Hypophosphatasia remains to be a very rare genetic disorder that is characterized by a mutation in ALPL gene. This leads to defective bone mineralization and causes multiple fractures and improper teeth development in early age. Although mostly a disease of the childhood, spontaneous relapse of the bone symptoms has been reported in late adult life. It has been noted that reduced bone density and fractures can recur during middle-age or late adulthood despite spontaneous remission in young adult life. Proper diagnosis and treatment is essential in these group of patients as bisphosphonate therapy is contraindicated.
A 61 year old female presented to her primary doctor with abnormally low alkaline phosphatase level of 17. Her son who is a teenager also had low alkaline phosphatase on a routine blood work which prompted further evaluation with genetic testing for ALPL gene mutation in all family members. Patient was diagnosed with Juvenile hypophasphatasia at the age of 60. Growing up, patient had multiple ankle and foot fractures in her childhood and teen years. She also had multiple cavities and premature teeth loss. As she became an adult, her fractures were less frequent. At the age of 55, she had another spontaneous wrist fracture as well. She was started on Strensiq by her primary care provider and referred to Endocrine clinic for further evaluation.
During her initial diagnosis her alkaline phosphatase was noted to be 17 and after the start of Strensiq it was at the level of 457. Her HLA b27 gene was negative. Her most recent bone scan showed bone mineral density at the level of spine with t-score of -1.8 and total hip t-score of -2.1. She was offered bisphosphonate therapy for osteoporosis by a previous provider but patient refused as she had researched on her disease entity and knew it is contraindicated.
Discussion : Juvenile hypophosphatasia is a rare disease of the pediatric population and it is even more rare to see it in adult population as a new diagnosis. This disease tends to have another peak in late adulthood after being silent in middle age group population. Our patient’s case is an example where such rare diagnosis becomes essential to recognize as the management therapy can significantly vary. It could have been dangerous for the patient to be started on bisphosphonate therapy. Fortunately this was avoided due to patient’s research and she was started on a novel therapy such as Strensiq.
Improper diagnosis and failure to recognize this disease entity can be detrimental to patient’s bone health. In 2015 FDA approved Strensiq- asfotase alfa which the first and only approved medical treatment for this disease entity.
University of Florida Department of Medicine
Endocrinology Fellow at University of Florida Jacksonville
Program Director, Endocrinology Fellowship
University of Florida College of Medicine - Jacksonville
Medical Education: University of Missouri, Columbia School of Medicine, Columbia, MO, USA
Residency: Internal Medicine, Washington University, St. Louis, MO, USA
Fellowship: Endocrinology, Diabetes and Metabolism, St Louis University School of Medicine, St. Louis, MO, USA