SUN-707 A Rare Case of Hypophosphatasia Presenting with Hypercalciuria

Abstract Disclosure: B. Singh: None. A.P. Amblee: None. Hypophosphatasia (HPP) is a rare bone mineralization disease which can present from childhood to adulthood. In the United States, it affects approximately 500-600 individuals per year. HPP is caused by inactivating mutations in the ALPL gene leading to buildup of inorganic pyrophosphate and impaired bone mineralization. Although generalized body pain, skeletal deformities, and dental abnormalities are the most common presenting features, approximately 20% of adults with HPP can present with renal abnormalities. Within this subgroup, 14% can present with hypercalcemia, hyperphosphatemia, or hypercalciuria. This case report is unique as the only feature found in a patient diagnosed with HPP was isolated hypercalciuria. A 51 year old male with HIV and chronic vitamin D deficiency was referred management of vitamin D deficiency . He was on bictegravir, emtricitabine, and tenofovir alafenamide for 14 years. He had no history of dental problems. He had a previous fracture of the tibia and wrist from a traumatic fall in his late 20s. Labs showed vitamin D was 19.78 ng/ml (normal range 30-100 ng/ml) , corrected calcium 8.9 mg/dl (normal range 8.7-10.4 mg/dl), alkaline phosphatase (AP) 40 U/L (normal range 45-117 U/L), and PTH 72 pg/mL (normal range 18-80.1 pg/ml). Thyroid studies and testosterone levels were within normal range. DXA scan showed normal bone mineral and low FRAX score. Vitamin D3 dosing was increased from 2000 to 5000 units daily. A secondary workup showed normal serum and urine protein electrophoresis, intact PTH, and celiac panel. He had an elevated 24-hour urine calcium level of 451 mg/24 hr. Due to the hypercalciuria, he was started on low dose hydrochlorothiazide. Vitamin D level normalized in 3 months ( 33 ng/ml)and AP remained low (38 U/L). Genetic testing for hypophosphatasia showed he was heterozygous for pathogenic variant in ALPL resulting in amino acid substitution p.Ala176Thr. Since this patient did not have any history of fractures, calcium and vitamin D supplementation was recommended. The unique feature is that he only presented with hypercalciuria which can have a long term risk for osteoporosis, kidney stone and chronic kidney disease . Due to heterogeneity in the presentation and disease course, HPP can be missed or underdiagnosed. Nonskeletal findings may be the main presenting factor in some adults, such as hypercalciuria in this case. Although more studies are required to look at the prevalence of isolated hypercalciuria in adult HPP patients, renal calcium abnormalities can be found in one fifth of HPP cases. HPP has a significantly negative effect on quality of life and early diagnosis with multidisciplinary interventions can help improve patient outcomes long term. Presentation: Sunday, July 13, 2025