GT-45

GRHPR

The GRHPR gene encodes the enzyme glyoxylate reductase/hydroxypyruvate reductase, which plays a crucial role in the metabolism of glyoxylate and hydroxypyruvate. This enzyme is involved in the detoxification of glyoxylate, converting it into glycolate, and in the reduction of hydroxypyruvate to D-glycerate. Mutations in the GRHPR gene can lead to a rare metabolic disorder known as Primary Hyperoxaluria Type 2 (PH2).

Function

The GRHPR enzyme is a member of the D-isomer specific 2-hydroxyacid dehydrogenase family. It catalyzes the NADPH-dependent reduction of glyoxylate to glycolate and hydroxypyruvate to D-glycerate. This activity is essential for the prevention of oxalate accumulation in the body, as excessive oxalate can lead to the formation of kidney stones and renal failure.

Genetic Information

The GRHPR gene is located on chromosome 9 at the cytogenetic band 9q12. It consists of 9 exons and spans approximately 10 kilobases. The gene is expressed in various tissues, with the highest levels found in the liver and kidneys.

Clinical Significance

Mutations in the GRHPR gene are associated with Primary Hyperoxaluria Type 2 (PH2), an autosomal recessive disorder characterized by the excessive production of oxalate. This condition can lead to recurrent kidney stones, nephrocalcinosis, and eventually renal failure if left untreated. Diagnosis of PH2 is confirmed through genetic testing and measurement of enzyme activity in liver biopsy samples.

Diagnosis and Management

Diagnosis of PH2 involves a combination of clinical evaluation, biochemical tests, and genetic analysis. Measurement of urinary oxalate and glycolate levels can provide initial clues, while genetic testing can confirm the presence of mutations in the GRHPR gene.

Management of PH2 focuses on reducing oxalate production and preventing kidney stone formation. This may include dietary modifications, increased fluid intake, and the use of medications such as potassium citrate to alkalinize the urine. In severe cases, liver transplantation may be considered to restore normal enzyme activity.

Research and Future Directions

Ongoing research aims to better understand the molecular mechanisms underlying GRHPR function and its role in oxalate metabolism. Gene therapy and enzyme replacement therapy are potential future treatments that are being explored to correct the underlying enzyme deficiency in PH2.

Also see

• Primary Hyperoxaluria
• Kidney Stones
• Metabolic Disorders
• Genetic Testing