6th February 2024

Oxalosis

Oxalosis, also known as primary hyperoxaluria, is a rare genetic disorder characterised by the overproduction and accumulation of oxalate in the body. Oxalate is naturally found in many foods but is a by-product of normal metabolism. In individuals with oxalosis, a defect in the enzyme responsible for oxalate breakdown and elimination leads to its build-up in various organs and tissues.

There are three main types of primary hyperoxaluria, each caused by mutations in different genes:

• Primary Hyperoxaluria Type 1
  • Mutations in the AGXT gene cause the most common and severe form of oxalosis. It leads to a deficiency of an enzyme called alanine glyoxylate aminotransferase (AGT), which is involved in the breakdown of glyoxylate, an oxalate precursor. Excess glyoxylate accumulates and is converted to oxalate, primarily in the kidney, forming calcium oxalate crystals. Over time, these crystals cause progressive kidney damage, chronic kidney disease, and end-stage renal disease.
• Primary Hyperoxaluria Type 2
  • It is caused by mutations in the GRHPR gene, which results in a deficiency of the enzyme glyoxylate/hydoxypyruvate reductase (GRHPR). Again, as a result, oxalate accumulates in the kidneys, but this form is generally less severe with later onset compared to type 1.
• Primary Hyperoxaluria Type 3
  • It is caused by mutations in the HOGA1 gene, resulting in the deficiency of the enzyme 4-hydroxy-2-oxoglutarate aldolase (HOGA1). The exact mechanisms of oxalate accumulation in this type are still being studied but appear to affect the kidneys.

Clinical features

Excessive oxalate accumulation can result in kidney stone formation and deposition of oxalate crystals in other organs and tissues, causing dysfunction. The affected organs include kidneys, urinary tract, heart, eyes, bones and central nervous system.

Diagnosis 

The diagnosis of oxalosis involves urine and blood sample analysis to measure oxalate levels, whilst genetic testing is helpful to identify the specific gene mutation involved.

Management

Treatment options for Oxalosis are limited. The mainstay of treatment is reducing oxalate levels to prevent further damage to kidneys and other organs. This involves increasing fluid intake, maintaining a low oxalate diet and using medications such as pyridoxine, which bind and eliminate excess oxalate from the body. In some cases, liver transplantation is considered to provide a functioning enzyme to help metabolise oxalate.