MON-754 - Investigating for Hypophosphatasia in A Young Female Athlete with Recurrent Stress Fractures

Background:

Hypophosphatasia is a rare genetic disorder characterized by low serum alkaline phosphatase (ALP) activity. This can often manifest as early loss of primary teeth, skeletal manifestations, including fractures or osteomalacia, with persistently low levels of ALP and elevation of natural substrates (PLP, PEA, PPi).. We present a case of a young female athlete with recurrent stress fractures, found to have persistently low levels of ALP, raising concern for hypophosphatasia.

Case Description:

A 20-year-old female initially presented to the clinic for evaluation of recurrent fractures. The patient was an avid runner who had a history of oligomenorrhea and multiple stress fractures. She did not have any family history of bone disorders. She had menarche at the age of 13 with regular menstrual cycles initially, but later developed oligomenorrhea for which she was placed on estrogen therapy with concern for hypothalamic amenorrhea. She had the return of normal menstruation after a lapse in running, however she still developed stress fractures one year later. At that time, her labs showed LH 3.9, FSH 1.5, estrogen 128, and ALP 40. ALP levels were checked multiple times over the course of the year with values ranging from 28-40. Further testing for possible causes of low ALP were all unremarkable including Zinc, Vitamin D, Magnesium, Phosphorus, Calcium, Vitamin B12, Vitamin C, Celiac panel, and Ceruloplasmin. DEXA scan revealed normal bone density. She also underwent genetic testing, which analyzed 67 genes associated with osteogenesis imperfecta and other causes of bone fragility, but was found to be unremarkable. Only Vitamin B6 was notably elevated at 24.6. Due to clinical suspicion of hypophosphatasia, supported by low ALP levels and elevated Vitamin B6, the decision was made to begin treatment with Strensiq (asfotase alfa).

Conclusion:

This case describes a patient with recurrent fractures and persistently low levels of ALP, with other workup largely unremarkable, raising concern for hypophosphatasia. Although the genetic testing conducted was unremarkable, hypophosphatasia is still possible given the overall clinical picture. Initially, this case with a young female athlete with oligomenorrhea may have been mistaken as a presentation of hypothalamic amenorrhea. However, with a thorough investigation and further workup, there appeared to be more to the picture. Following this patient for the next several months will be paramount to determine the response to treatment with the ultimate goal of decreasing her risk of future stress fractures.

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