R2HG

R2HG is a gene that provides instructions for making a protein called argininosuccinate lyase (ASL). This enzyme is crucial for a metabolic pathway known as the urea cycle. The urea cycle is the primary mechanism by which the body removes excess nitrogen, a byproduct of protein breakdown, converting it into urea, which is then excreted in urine. ASL plays a key role in the later stages of this cycle, catalyzing the breakdown of argininosuccinate into arginine and fumarate. Arginine is an essential amino acid, and fumarate is an intermediate in both the urea cycle and the citric acid cycle, indicating a connection between these two vital metabolic processes.

Mutations in the R2HG gene can lead to argininosuccinate lyase deficiency, a rare genetic disorder. This deficiency impairs the urea cycle, causing a buildup of toxic nitrogenous compounds in the blood, a condition known as hyperammonemia. Symptoms can vary in severity and may include neurological problems such as intellectual disability, seizures, and developmental delays. In severe cases, hyperammonemia can be life-threatening. Diagnosis typically involves biochemical testing to measure levels of specific amino acids and organic acids in the blood and urine, often followed by genetic testing to identify mutations in the R2HG gene. Treatment focuses on managing ammonia levels through dietary restrictions and, in some cases, medications.