PH is a family of rare genetic disorders causing hepatic oxalate overproduction that can result in kidney damage and in some cases life-threatening systemic disease. Although PH Type 1 (PH1) is the most well known, all PH subtypes are likely underdiagnosed.8,9
Although PH primarily manifests as a kidney disease, it originates with an enzyme deficiency in the liver. This enzyme deficiency results in a buildup of glyoxylate, which is converted to excessive amounts of oxalate by hepatic LDH.8,10
In a study, approximately 15% of patients with early-onset kidney stones or recurrent kidney stones have a causative monogenic condition. Gene-specific analysis can be pivotal for accurate diagnosis.11
PH1, PH2, and PH3 are all linked to kidney stones and burdensome stone removal procedures, with 70% of patients requiring one or more urologic procedures during their lifetime. In more advanced cases, PH patients may require frequent dialysis and a dual liver-kidney transplant.8,12-22
Edvardsson VO et al. Hereditary causes of kidney stones and chronic kidney disease. Pediatr Nephrol. 2013;28(10):1923-1942.
Bhasin B et al. Primary and secondary hyperoxaluria: understanding the enigma. World J Nephrol. 2015;4(2):235-244.
Harambat J et al. Genotype-phenotype correlation in primary hyperoxaluria type 1: the p.Gly170Arg AGXT mutation is associated with a better outcome. Kidney Int. 2010;77(5):443-449.
van Woerden CS et al. Primary hyperoxaluria type 1 in The Netherlands: prevalence and outcome. Nephrol Dial Transplant. 2003;18(2):273-279.
Frishberg Y et al. Intra-familial clinical heterogeneity: absence of genotype-phenotype correlation in primary hyperoxaluria type 1 in Israel. Am J Nephrol. 2005;25(3):269-275.
Birtel J et al. The Ocular Phenotype in Primary Hyperoxaluria Type 1. Am J Ophthalmol. 2019;206:184-191.
Mandrile G et al. Data from a large European study indicate that the outcome of primary hyperoxaluria type 1 correlates with the AGXT mutation type. Kidney Int. 2014;86(6):1197-1204.
Cochat P, Rumsby G. Primary hyperoxaluria. N Engl J Med. 2013;369(7):649-658.
Hopp K et al. Phenotype-genotype correlations and estimated carrier frequencies of primary hyperoxaluria. J Am Soc Nephrol. 2015;26(10):2559-2570.
Lai C et al. Specific inhibition of hepatic lactate dehydrogenase reduces oxalate production in mouse models of primary hyperoxaluria. Mol Ther. 2018;26(8):1983-1995.
Halbritter J, Seidel A, Müller L, et al. Update on hereditary kidney stone disease and introduction of a new clinical patient registry in Germany. Front Pediatr. 2018;6:47. doi: 10.3389/fped.2018.00047
Tang X et al. Nephrocalcinosis is a risk factor for kidney failure in primary hyperoxaluria. Kidney Int. 2015;87(3):623-631.
Milliner DS et al. Phenotypic expression of primary hyperoxaluria: comparative features of types I and II. Kidney Int. 2001;59(1):31-36.
Takayama T et al. Ethnic differences in GRHPR mutations in patients with primary hyperoxaluria type 2. Clin Genet. 2014;86(4):342-348.
Johnson SA et al. Primary hyperoxaluria type 2 in children. Pediatr Nephrol. 2002;17(8):597-601.
Garrelfs SF et al. Patients with primary hyperoxaluria type 2 have significant morbidity and require careful follow-up. Kidney Int. 2019;96(6):1389-1399.
Fang X et al. Nine novel HOGA1 gene mutations identified in primary hyperoxaluria type 3 and distinct clinical and biochemical characteristics in Chinese children. Pediatr Nephrol. 2019;34(10):1785-1790.
Williams EL et al. The enzyme 4-hydroxy-2-oxoglutarate aldolase is deficient in primary hyperoxaluria type 3. Nephrol Dial Transplant. 2012;27(8):3191-3195.
Allard L et al. Renal function can be impaired in children with primary hyperoxaluria type 3. Pediatr Nephrol. 2015;30(10):1807-1813.
Monico CG et al. Primary hyperoxaluria type III gene HOGA1 (formerly DHDPSL) as a possible risk factor for idiopathic calcium oxalate urolithiasis. Clin J Am Soc Nephrol. 2011;6(9):2289-2295.
Danese D et al. Understanding the burden of primary hyperoxaluria type 1 (PH1): a survey of physician experiences with PH1. Poster presented at: IPNA 18th Congress; October 17-21, 2019; Venice, Italy.
Wang W et al. Mutation hot spot region in the hoga1 gene associated with primary hyperoxaluria type 3 in the Chinese population. Kidney Blood Press Res. 2019;44(4):743-753.
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