Primary hyperoxaluria

Overview of primary hyperoxaluria, a rare genetic disorder

Primary Hyperoxaluria

Structure of oxalate, a key compound involved in primary hyperoxaluria

Primary hyperoxaluria is a rare genetic disorder characterized by the overproduction of oxalate, a type of organic acid that combines with calcium to form calcium oxalate crystals. These crystals can accumulate in the kidneys and other organs, leading to kidney stones, nephrocalcinosis, and eventually renal failure.

Pathophysiology

Primary hyperoxaluria is caused by mutations in genes responsible for the metabolism of glyoxylate, a precursor to oxalate. The most common form, primary hyperoxaluria type 1, is due to mutations in the AGXT gene, which encodes the enzyme alanine-glyoxylate aminotransferase. This enzyme is crucial for converting glyoxylate to glycine, preventing its conversion to oxalate.

Types

There are three main types of primary hyperoxaluria:

• Primary hyperoxaluria type 1 (PH1): Caused by mutations in the AGXT gene.
• Primary hyperoxaluria type 2 (PH2): Caused by mutations in the GRHPR gene, affecting the enzyme glyoxylate reductase/hydroxypyruvate reductase.
• Primary hyperoxaluria type 3 (PH3): Caused by mutations in the HOGA1 gene, affecting the enzyme 4-hydroxy-2-oxoglutarate aldolase.

Symptoms

The symptoms of primary hyperoxaluria can vary but often include:

• Recurrent kidney stones
• Hematuria (blood in urine)
• Urinary tract infections
• Nephrocalcinosis
• Renal failure

Diagnosis

Diagnosis of primary hyperoxaluria involves:

• Measurement of oxalate levels in urine and plasma
• Genetic testing to identify mutations in the relevant genes
• Kidney imaging to detect stones or nephrocalcinosis

Treatment

Treatment strategies for primary hyperoxaluria include:

• High fluid intake to dilute urine
• Use of potassium citrate to inhibit stone formation
• Pyridoxine (vitamin B6) supplementation, particularly in PH1
• Liver transplantation in severe cases, especially for PH1
• Kidney transplantation in cases of renal failure

Prognosis

The prognosis for individuals with primary hyperoxaluria varies depending on the type and severity of the disease. Early diagnosis and management can improve outcomes, but many patients may eventually require dialysis or transplantation.

Related pages

• Kidney stone
• Genetic disorder
• Renal failure