7293 An Unusual Case Of Adult-Onset Heterozygous HHRH In A Male With Normal Phosphorus And Severe Osteoporosis

Abstract Disclosure: M. El Najjar: None. A. Sabet: None. D. Willard: None. Introduction: Hereditary hypophosphatemic rickets with hypercalciuria (HHRH) is a rare genetic disorder characterized by renal phosphate wasting, which can affect bone metabolism. Although onset is typically in childhood, adult-onset forms have been described, and the manifestation depends on the zygosity of each patient. Most commonly, adults with HHRH demonstrate markedly reduced bone density and multiple fractures. Heterozygotes have milder presentations with mild hypophosphatemia, hypercalciuria, and nephrolithiasis, usually without bone disease; however, it is less well characterized. Case report: A 73-year-old man suffered an L1 vertebral compression fracture while playing golf. Bone mineral density testing revealed T-scores of -0.9 at the lumbar spine and -3.4 at the femoral neck (Z-score -2.6). He started alendronate 70 mg weekly for osteoporosis treatment. A year later, the patient sustained an L3 vertebral compression fracture while on treatment with no improvement in his bone density. His family history was remarkable for osteoporosis in his mother but no nephrolithiasis or hypercalcemia. Physical examination was unremarkable. Laboratory evaluation was notable for a 1,25-dihydroxyvitamin D of 87 pg/mL (18-72 pg/mL) , a 24-hour urine calcium of 240 mg/g Cr (30-210 mg/g),a serum PTH of 9 pg/mL (16-77 pg/ml) , but otherwise a normal serum calcium level of 9.4 mg/dL (8.6-10.3 mg/dL) and serum phosphate level of 2.2 mg/dl (2.1-4.3 mg/dl). Genetic testing revealed heterozygosity for SLC34A3 mutation, which is associated with HHRH. The patient discontinued alendronate and started 250 mg phosphorus supplementation 4 times daily. At 6 months follow up, he reported improvement in his body aches, and biochemical testing showed normalization of his 24-hour urine calcium to 171 mg/g Cr and serum PTH to 21 pg/mL. Repeat bone density scan after 1 year of phosphorus supplementation showed T-scores of -0.3 at the lumbar spine (5.8% increase) and -2.6 at the femoral neck (15.5% increase). Clinical Lesson: HHRH is an autosomal recessive hypophosphatemic rickets associated with mutations of the SLC34A3 sodium-phosphate cotransporter, where it is believed that selective phosphate wasting leads to increased calcitriol, in contrast to other forms of hypophosphatemic rickets, causing increased intestinal calcium absorption and resulting hypercalciuria. Adult-onset forms of HHRH have been described in heterozygous carriers of the SLC34A3 mutation and usually present with low to low-normal phosphate levels, hypercalciuria, and nephrolithiasis but without bone disease. However, clinical variations of heterozygous carriers have also been recognized, and therefore are likely underdiagnosed. Our patient’s serum phosphorus level was within the normal range, and hypophosphatemic rickets could have been missed if a more extensive laboratory evaluation had not been performed. Presentation: 6/1/2024