Journal Article

SUN-756 Diagnosing and Treating Hereditary Hypophosphatemia Rickets with Hypercalciuria

Al-Khayer, Fadi Alarab, Dickerman, Sarah

2025

Overview

Abstract Disclosure: S. Dickerman: None. F.A. Al-Khayer: None. Introduction: Hereditary hypophosphatemia rickets with hypercalciuria (HHRH) is a rare autosomal recessive disorder with an estimated prevalence of 1 in 250,000 caused by mutations in the SLC34A3 gene that clinically manifests as rickets, bone pain, and hypercalciuria. This disorder may present similarly to more common disease states such as osteomalacia or osteoporosis, making its diagnose difficult and often tenuous. Clinical Case: This is the case of a 39-year-old female patient with a complex past medical history significant for renal stones since childhood and pancreatoduodenectomy in 2022 due to a dysplastic pancreatic lesion who initially presented to the office in 2024 with low phosphate, normal alkaline phosphatase, normal B6, high calcitriol, and hypercalciuria. Initial diagnoses considered based on these results included Fanconi syndrome, x-linked hypophosphatemia, nutritional or tumor-induced osteomalacia, and hereditary Vitamin D resistance. However, none of these conditions were consistent with her presenting symptoms and lab values. To work up the etiology of her presentation, the tubular reabsorption of phosphorus (TRP) was calculated using TRP=100(1-[quarinePO4/UCr])(serum Cr/serum PO4). When serum phosphate is low, it is expected that renal phosphate absorption and TRP will increase, yet this patient had a calculated TRP of 15. The tubular maximum reabsorption of phosphate (TmP) was then calculated using TmP=(TRP)(serum PO4), yielding 27. The ratio of TmP/eGFR was calculated to be 0.4, with a normal ratio for females being 3-4.45, 5-4 standard deviations below the age-related mean. Further, the upper limit of normal calcium excretion in 24 hours is 4mg/kg and this patient’s excretion was calculated to be 9.4mg/kg. An excretion rate greater than 8.6mg/kg is consistent with HHRH, as is the low ratio of Tmp/eGFR. The patient was treated with potassium phosphate supplementation. This successfully led to the correction of all the above abnormalities except for the decreased TmP/eGFR ratio and improvement of her symptoms. The diagnosis was later confirmed by detecting the pathogenic SLC34A3 mutation. Conclusion: Making the diagnosis of HHRH is challenging and requires an extensive and often timely workup. This case details the diagnostic process and key findings associated with HHRH: phosphate wasting which causes an appropriately elevated level of calcitriol, increased calcium intestinal absorption, suppression of PTH, hypercalciuria, and phosphate deficiency acting as a potent and direct stimulus to renal 25-hydroxyvitamin D-1-alpha hydroxylase (CYP27B1) activity. Treatment of HHRH and correction of these abnormalities may be accomplished utilizing phosphate supplementation. This case report offers a diagnostic schema for making an obscure diagnosis. Presentation: Sunday, July 13, 2025

• Publisher: Oxford University Press
• Subject: Rickets