Mutations in the genes AGXT  and GRHPR cause PH1 and PH2, respectively, through decreased production or activity of the proteins they make, which stops the normal breakdown of glyoxylate. Similarly, mutations in the gene HOGA1 cause PH3 due to loss-of-function mutations resulting in impaired protein function.PH1 is considered to be the most common and rapidly progressing form, accounting for about 80% of all currently diagnosed cases and PH2 and PH3 accounting for approximately 10% each of the current cases. However, recent evidence has suggested that PH2 and PH3 are not as benign as previously thought, with up to 50% of patients with PH2 developing kidney failure (chronic kidney disease [CKD] stage 5). While current estimates indicate that kidney failure is rarer in patients with PH3 compared to PH1 and PH2, CKD has been reported in patients with PH3. Moreover, the genetic prevalence based on known PH3 variants is much higher than the diagnosed prevalence of the disease, which could mean either incomplete penetrance (i.e. variant present with no clinical symptoms) or underdiagnosis (i.e. variant present with clinical symptoms but not diagnosed). Treatment
Increased water intake and alkalinization of urine is advised to prevent oxalate precipitation in urinary tract. In addition, Vitamin B6 (pyridoxine) is used to treat PH1 because alanine glyoxylate transaminase requires pyridoxine as cofactor. In approximately one third of patients with PH1, pyridoxine treatment decreases oxalate excretion and prevent kidney stone formation.
Conversely, a restriction in oxalate intake is of limited use as the main source of oxalate is endogenous in primary hyperoxaluria.Lumasiran, an RNA interference therapeutic drug, is indicated for the treatment of primary hyperoxaluria type 1 (PH1) in adults and children of all ages and is available under the UK Early Access to Medicines Scheme (EAMS). Lumasiran was approved for medical use in the European Union and in the United States in November 2020. In addition, there are a few agents under investigation in clinical trials for PH: Nedosiran (RNA interference therapeutic) for PH1, PH2, and PH3; Stiripentol (antiepileptic drug); Oxabact (lyophilized Oxalobacter formigenes; and Reloxaliase (oxalate-digesting enzyme) for PH

Treatment of renal failure in primary hyperoxaluria
Kidney failure is a serious complication requiring treatment in its own right. Dialysis can control kidney failure but tends to be inadequate to dispose of excess oxalate. Renal transplant is more effective and is the primary treatment of severe hyperoxaluria. Ultimately though, liver transplantation (often in addition to renal transplant) is required to correct the underlying metabolic defect. See also
Peroxisomal disorder

References
External links

GeneReview/NCBI/NIH/UW entry on Primary Hyperoxaluria Type 1
GeneReview/NCBI/NIH/UW entry on Primary Hyperoxaluria Type 2
Primary hyperoxaluria (A service of the U.S. National Library of Medicine)