SNP Shot: Genomic Insights

Primary hyperoxaluria is a rare condition characterized by the recurrent development of kidney and bladder stones. End-stage renal disease (ESRD), a life-threatening condition where the kidneys fail to effectively remove waste and excess fluid from the blood, is a common and serious outcome.

Primary hyperoxaluria arises from an overproduction of oxalate within the body. Healthy kidneys filter oxalate, which is then excreted in urine. However, in individuals with primary hyperoxaluria, urinary oxalate levels are abnormally high (hyperoxaluria). During excretion, oxalate can bind with calcium to form calcium oxalate, the main component of kidney and bladder stones. These calcium oxalate deposits can injure the kidneys and other organs, leading to blood in the urine (hematuria), urinary tract infections, kidney damage, ESRD, and damage to other organs. As the disease progresses, the kidneys' ability to remove oxalate diminishes, resulting in oxalate accumulation in the bloodstream. This excess oxalate is then deposited in tissues throughout the body (systemic oxalosis), notably in bones and blood vessel walls. Oxalosis in bones can result in fractures.

Primary hyperoxaluria presents in three distinct forms, each with varying levels of severity and different underlying genetic causes. In primary hyperoxaluria type 1, kidney stones typically emerge between childhood and young adulthood, and ESRD can develop at any point in life. Primary hyperoxaluria type 2 resembles type 1, but ESRD typically occurs later in life. Individuals with primary hyperoxaluria type 3 generally experience kidney stones early in childhood; however, due to the limited number of documented cases, other associated symptoms and signs are not well-defined.

Inheritance:

This condition follows an autosomal recessive inheritance pattern. This means that for the condition to become apparent, both copies of the responsible gene in each cell must carry a mutation. Typically, the parents of a child affected by an autosomal recessive condition each carry one copy of the mutated gene, but they usually do not show any signs or symptoms of the disorder.