N-Acetylglutamate synthase deficiency

N-Acetylglutamate synthase deficiency (NAGS deficiency) is a rare genetic disorder that affects the urea cycle, a series of biochemical reactions that occur in the liver to remove ammonia from the blood. This condition is characterized by a deficiency of the enzyme N-acetylglutamate synthase (NAGS), which is essential for the production of N-acetylglutamate (NAG). NAG is a critical activator of carbamoyl phosphate synthetase I (CPS1), the first enzyme in the urea cycle.

Pathophysiology

NAGS deficiency leads to a disruption in the urea cycle, resulting in the accumulation of ammonia in the blood, a condition known as hyperammonemia. Ammonia is toxic to the central nervous system and can cause a range of symptoms, from mild to severe, including lethargy, vomiting, seizures, coma, and even death if left untreated.

Genetics

NAGS deficiency is inherited in an autosomal recessive pattern, meaning that an individual must inherit two copies of the defective gene, one from each parent, to be affected by the disorder. The gene responsible for NAGS deficiency is located on chromosome 17.

Symptoms

The symptoms of NAGS deficiency can vary widely but often include:

• Hyperammonemia
• Lethargy
• Vomiting
• Seizures
• Coma
• Developmental delay
• Intellectual disability

Diagnosis

Diagnosis of NAGS deficiency typically involves a combination of clinical evaluation, biochemical testing, and genetic testing. Elevated levels of ammonia in the blood, along with low levels of citrulline and arginine, may suggest a urea cycle disorder. Genetic testing can confirm the diagnosis by identifying mutations in the NAGS gene.

Treatment

Treatment for NAGS deficiency focuses on managing hyperammonemia and preventing its recurrence. This may include:

• Dietary management to limit ammonia production
• Medications such as ammonia scavengers (e.g., sodium phenylbutyrate)
• Supplementation with N-carbamylglutamate (NCG), a synthetic analog of NAG, to activate CPS1

Prognosis

The prognosis for individuals with NAGS deficiency varies depending on the severity of the condition and the effectiveness of treatment. Early diagnosis and prompt treatment are crucial for preventing severe complications and improving outcomes.

See also

• Urea cycle disorder
• Hyperammonemia
• Genetic disorder
• Metabolic disorder