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Abstract: FR-PO590

Genetic Prevalence Estimates for All Types of Primary Hyperoxaluria

Session Information

Category: Genetic Diseases of the Kidneys

  • 1202 Genetic Diseases of the Kidneys: Non-Cystic


  • Mandrile, Giorgia, Azienda Ospedaliero Universitaria San Luigi Gonzaga, Orbassano, Piemonte, Italy
  • Rumsby, Gill, UCL Hospitals, Kintbury, United Kingdom
  • Sciannameo, Veronica, Universita degli Studi di Torino Scuola di Medicina, Torino, Piemonte, Italy
  • Harris, Peter C., Mayo Clinic Minnesota, Rochester, Minnesota, United States
  • Lieske, John C., Mayo Clinic Minnesota, Rochester, Minnesota, United States
  • Glover, Michelle, Novo Nordisk Inc, Plainsboro, New Jersey, United States

Primary hyperoxaluria is a rare disorder caused by biallelic pathogenic changes in 3 known genes (AGXT (PH1), GRHPR (PH2), HOGA1 (PH3)). Affected patients have marked hyperoxaluria, frequent kidney stones, and are at high risk for kidney failure. Patients are often diagnosed late after they have developed severe disease complications, including systemic oxalosis. Given approved and emerging therapies for these diseases, it is important to understand the genetic prevalence of PH to determine the magnitude of missed diagnoses/reduced penetrance and develop strategies to improve patient outcomes.


Variants from all 3 genes were curated from OxalEurope, Rare Kidney Stone Consortium, ClinVar, and GnomAD registries in addition to an extensive literature review. Variants were scored as Pathogenic or Likely Pathogenic according to the 2015 ACMG guidelines using Intervar. Allelic frequencies were determined from GnomADv.2.1.1 after all identified variants were curated/reclassified and used to calculate the lifetime genetic prevalence of disease.


The number of Pathogenic or Likely Pathogenic variants studied following comprehensive curation or reclassification of variants were 89 AGXT, 45 GRHPR, and 74 HOGA1. The following overall estimated genetic prevalence was determined: PH1 (1:209,357), PH2 (1:863,028), and PH3 (1:90,834) resulting in an estimated 17 per 1M individuals (136,000 individuals worldwide) with a lifetime possibility of developing PH regardless of ethnicity. The estimated carrier frequency is the following: PH1 (1:229), PH2 (1:465), and PH3 (1:151). Furthermore, ethnic groups were examined using post-curated variants showing the genetic prevalence is most predominant for PH1, PH2, and PH3 in the following populations respectively: East Asian (1:84,574), South Asian (1:390,788), and Ashkenazi Jewish (1:5,633).


Based on analysis of available genetic data, the estimated lifetime prevalence of PH is approximately 1:58,823 individuals globally. This is more common than currently diagnosed by at least an order of magnitude. The extent to which this is due to reduced disease penetrance or underdiagnosis is to be determined. Increasing access to diagnostic testing and continued curation of variants to the ClinVar registry is important to improve outcomes for all patients.


  • Commercial Support – Dicerna Pharmaceuticals Inc., a Novo Nordisk Company