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Abstract: PO1203

High Prevalence of Kidney Cysts in Hereditary Hypophosphatemic Rickets with Hypercalciuria

Session Information

Category: Genetic Diseases of the Kidneys

  • 1001 Genetic Diseases of the Kidneys: Cystic

Authors

  • Hanna, Christian, Mayo Clinic Minnesota, Rochester, Minnesota, United States
  • Arroyo, Jennifer, Mayo Clinic Minnesota, Rochester, Minnesota, United States
  • Tebben, Peter, Mayo Clinic Minnesota, Rochester, Minnesota, United States
  • Torres, Vicente E., Mayo Clinic Minnesota, Rochester, Minnesota, United States
  • Harris, Peter C., Mayo Clinic Minnesota, Rochester, Minnesota, United States
  • Goldfarb, David S., NYU Langone Health, New York, New York, United States
  • Sas, David J., Mayo Clinic Minnesota, Rochester, Minnesota, United States
  • Milliner, Dawn S., Mayo Clinic Minnesota, Rochester, Minnesota, United States
  • Lieske, John C., Mayo Clinic Minnesota, Rochester, Minnesota, United States
  • Chebib, Fouad T., Mayo Clinic Minnesota, Rochester, Minnesota, United States
  • Potretzke, Theodora A., Mayo Clinic Minnesota, Rochester, Minnesota, United States
Background

Hereditary Hypophosphatemic Rickets with Hypercalciuria (HHRH) is a rare monogenic disorder caused by SLC34A3 pathogenic variants, characterized by renal phosphate wasting, hypophosphatemia, hypercalciuria (HC), elevated 1,25-dihydroxyvitamin D, nephrocalcinosis (NC), and urinary stone disease (USD). Previously we reported a high prevalence of kidney cysts in CYP24A1 deficiency. Thus, in the current study, we characterized cyst presence in HHRH, another monogenic cause of HC, NC, and USD.

Methods

Medical records from Mayo Clinic and Rare Kidney Stone Consortium research results were queried for all patients with genetically confirmed HHRH diagnosis. Clinical characteristics and imaging data are summarized in table 1.

Results

Among 12 patients with SLC34A3 pathogenic variants (7 monoallelic, 5 biallelic), 42% (5/12) were males. Median age at clinical presentation was 17 yrs (range 8-46) and at genetic confirmation 42 yrs (range 9-66). None had a family history of cystic kidney disease. Kidney cysts (Figure 1) were present in 75% (9/12), among whom median age at first kidney imaging and first cyst detection was 41 yrs (range 9-64). Median number of cysts per patient was 3 (range 1-23). The number of cysts ≥ 5 mm in size was above the 97.5th percentile of an age- and sex-matched control population in 6/9 (67%). At least 2 cysts ≥ 5 mm in size were found in 100% of children.

Conclusion

We found a strong association between HHRH and kidney cysts. Similarities in the biochemical profiles of HHRH and CYP24A1 deficiency suggest elevated active vitamin D, and/or HC may be potential factors in cyst formation. Further studies are needed to evaluate the role of the SLC34A3 gene in cyst formation.

Funding

  • Other NIH Support