An Uncommon Case of Hypophophatasia Presenting With Galactorrhea, Diagnosed at a Later Age Than Expected

Hypophosphatasia is a rare genetic disorder which causes accumulation of inorganic pyrophosphate that in turn inhibits mineralization. It is caused by a mutation in the non-specific alkaline phosphatase gene (TNSALP). We will review the diagnosis during adulthood when the presentation is characterized by poor healing, recurrent metatarsal stress fractures and bone pain. We are reporting the case of a 38-year-old white female with history of Melanoma referred to the Pituitary Clinic due to galactorrhea. During the encounter it was noted that she had history of disseminated joint pain, myalgias, periodontal complications as well as biochemical evidence of low alkaline phosphatase. At age three she had premature teeth loss, and clumsy gait, which later resolved. She was evaluated for this and diagnosed with odontohypophophatasia at which time no treatment was initiated. As an adult patient had two non-traumatic ankle fractures with associated frail teeth, chipping, and cracking without significant trauma. At around 36 years of age, patient started developing worsening joint pain, stiffness, myalgias and 35 pounds weight gain. Family History is remarkable for her father, having history of low alkaline phosphate and odontogenic infections with no joint or muscle pain. Paternal grandmother had history of dental infections and frail teeth. The patient has four sons; her oldest son has low alkaline phosphate with no clinical symptoms. Patient’s biochemical analysis was unremarkable except for low alkaline phosphate range between 25–38 U/L (40–125 U/L) and elevated Vitamin B6 69.5 ng/mL (2.1–21.7 ng/mL). The physical exam was unremarkable. Brain MRI showed a 3 mm microadenoma with normal pituitary hormonal workup, including diluted prolactin. Mammogram did not show any abnormalities. It was determined that the pituitary microadenoma was non-functioning, and galactorrhea was not hormonal mediated. The patient was referred to a genetic specialist for evaluation of Hypophosphatasia. Testing for TNSALP mutation was done which showed an ALP Mutation variant c.1172G>A (p. Arg391His). She was started on asfotase alfa (Strensiq) an enzyme replacement for Hypophosphatasia, in November 2019. Hypophosphatasia is a rare condition often diagnosed during early life. Due to wide number of possible mutations in the TNSALP gene, the clinical presentation can vary between patients and diagnosis can be elusive. In our patient, despite being diagnosed with odontohypophophatasia at an early age, and having many periodontal complications, hypophosphatasia was not confirmed until more than 30 years after the initiation of symptoms. In the management of Hypophosphatasia, having an accurate timely diagnosis can provide patients with early intervention of advanced treatment modalities such as Strensiq that can improve symptoms.