What are the genetic changes related to primary hyperoxaluria ?
Mutations in the AGXT, GRHPR, and HOGA1 genes cause primary hyperoxaluria types 1, 2, and 3, respectively. These genes provide instructions for making enzymes that are involved in the breakdown and processing of protein building blocks (amino acids) and other compounds. The enzyme produced from the HOGA1 gene is involved in the breakdown of an amino acid, which results in the formation of a compound called glyoxylate. This compound is further broken down by the enzymes produced from the AGXT and GRHPR genes.  Mutations in the AGXT, GRHPR, or HOGA1 gene lead to a decrease in production or activity of the respective proteins, which prevents the normal breakdown of glyoxylate. AGXT and GRHPR gene mutations result in an accumulation of glyoxylate, which is then converted to oxalate for removal from the body as a waste product. HOGA1 gene mutations also result in excess oxalate, although researchers are unsure as to how this occurs. Oxalate that is not excreted from the body combines with calcium to form calcium oxalate deposits, which can damage the kidneys and other organs.