Which are the causes of Arginase Deficiency/Argininemia?

Arginase deficiency, also known as argininemia, is a rare genetic disorder that affects the urea cycle, a metabolic pathway responsible for removing toxic ammonia from the body. This condition is caused by a mutation in the ARG1 gene, which provides instructions for producing the enzyme arginase.

Arginase is an essential enzyme that plays a crucial role in the urea cycle. It is responsible for the final step of converting the amino acid arginine into urea and ornithine. Urea is then excreted in urine, while ornithine is recycled back into the urea cycle. In individuals with arginase deficiency, the enzyme is either absent or not functioning correctly, leading to the accumulation of arginine and ammonia in the blood.

The causes of arginase deficiency are primarily genetic. The condition follows an autosomal recessive pattern of inheritance, meaning that an affected individual must inherit two copies of the mutated ARG1 gene, one from each parent. If both parents are carriers of the mutated gene, there is a 25% chance with each pregnancy that their child will have arginase deficiency.

Common symptoms of arginase deficiency include intellectual disability, developmental delay, seizures, spasticity, and progressive loss of neurological function. These symptoms are primarily caused by the toxic buildup of ammonia in the brain, which can lead to brain damage if left untreated.

Diagnosis of arginase deficiency is typically made through newborn screening programs, which test for elevated levels of arginine and ammonia in the blood. Confirmatory testing involves genetic analysis to identify mutations in the ARG1 gene.

Treatment for arginase deficiency focuses on managing the symptoms and preventing the buildup of ammonia. This often involves a low-protein diet, which restricts the intake of arginine and other amino acids that can be converted into ammonia. Medications such as nitrogen-scavenging drugs may also be prescribed to help remove excess ammonia from the body.

Research into potential gene therapies and enzyme replacement therapies is ongoing, with the aim of providing more targeted and effective treatments for individuals with arginase deficiency.