Hyperoxaluria type 1

Hyperoxaluria Type 1

Hyperoxaluria Type 1 is a rare genetic disorder characterized by the overproduction of oxalate, a substance that combines with calcium to form kidney stones. This condition is caused by a deficiency of the liver enzyme alanine-glyoxylate aminotransferase (AGT), which is crucial for the detoxification of glyoxylate, a precursor of oxalate.

Pathophysiology

In individuals with Hyperoxaluria Type 1, mutations in the AGXT gene lead to a deficiency or malfunction of the AGT enzyme. This enzyme is normally located in the peroxisomes of liver cells, where it converts glyoxylate to glycine. When AGT is deficient, glyoxylate is instead converted to oxalate, which is then excreted in the urine. The excessive oxalate combines with calcium to form calcium oxalate crystals, leading to the formation of kidney stones and potential kidney damage.

Clinical Presentation

Patients with Hyperoxaluria Type 1 often present with recurrent kidney stones, nephrocalcinosis, and progressive renal failure. Symptoms may include:

• Flank pain
• Hematuria (blood in urine)
• Urinary tract infections
• Decreased kidney function

In severe cases, systemic oxalosis can occur, where oxalate deposits in other tissues such as bones, joints, and the heart.

Diagnosis

Diagnosis of Hyperoxaluria Type 1 involves:

• Measurement of urinary oxalate levels
• Genetic testing for mutations in the AGXT gene
• Liver biopsy to assess AGT enzyme activity (less commonly performed)

Treatment

Management of Hyperoxaluria Type 1 focuses on reducing oxalate production and preventing kidney damage. Treatment options include:

• High fluid intake to dilute urine and reduce stone formation
• Dietary modifications to limit oxalate intake
• Vitamin B6 (pyridoxine) supplementation, which can enhance residual AGT activity in some patients
• Liver transplantation, which can correct the underlying enzyme deficiency
• Kidney transplantation in cases of end-stage renal disease

Prognosis

The prognosis for individuals with Hyperoxaluria Type 1 varies depending on the severity of the enzyme deficiency and the effectiveness of treatment. Early diagnosis and management are crucial to prevent kidney damage and systemic oxalosis.

Also see

• Primary hyperoxaluria
• Kidney stone disease
• Genetic disorders
• Metabolic disorders