A diagnosis of<unk>  is suspected based on presenting patient characteristics such as kidney stones in infants or children, recurrent kidney stones in adults, or family history of<unk> . In these patients, stone analysis and urine analysis are recommended to rule out secondary causes of<unk> . A definitive diagnosis of<unk>  requires genetic testing. This is performed using a gene panel covering known mutations for all three types of<unk> . Classification The three main types of<unk>  <unk> , PH2, and PH3) are each associated with mutations in specific genes involved in the metabolism of glyoxylate, the precursor of oxalate. These mutations result in decreased production or activity of the proteins that are involved in the normal breakdown of glyoxylate, which results in an overproduction of oxalate. Mutations in the genes AGXT and GRHPR cause<unk>  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.<unk>  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<unk>  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). Type OMIM Gene<unk>  AGXT PH2 GRHPR PH3 HOGA1
Primary hyperoxaluria
Hawkinsinuria
Cystinuria
Alkaptonuria
Alpha-aminoadipic and alpha-ketoadipic aciduria
Trimethylaminuria
Aspartylglucosaminuria
Homocystinuria