Which are the symptoms of N-Acetylglutamate Synthetase Deficiency?

N-Acetylglutamate Synthetase Deficiency (NAGS deficiency) is a rare genetic disorder that affects the body's ability to produce an enzyme called N-acetylglutamate synthetase. This enzyme plays a crucial role in the urea cycle, which is responsible for removing toxic ammonia from the body. Without sufficient levels of N-acetylglutamate synthetase, ammonia builds up in the blood, leading to a range of symptoms and potentially life-threatening complications.

Symptoms of N-Acetylglutamate Synthetase Deficiency:

1. Hyperammonemia: The hallmark symptom of NAGS deficiency is elevated levels of ammonia in the blood, known as hyperammonemia. Ammonia is a neurotoxin that can cause significant damage to the brain and nervous system. Hyperammonemia can lead to symptoms such as:

• Seizures


• Lethargy


• Confusion


• Irritability


• Behavioral changes


• Coma (in severe cases)

2. Vomiting and Feeding Difficulties: Infants with NAGS deficiency often experience frequent vomiting and have difficulty feeding. These symptoms can lead to poor weight gain and failure to thrive.

3. Intellectual Disability: If left untreated, NAGS deficiency can cause progressive damage to the brain, resulting in intellectual disability. Children may experience developmental delays, learning difficulties, and impaired cognitive function.

4. Neurological Symptoms: In addition to seizures, individuals with NAGS deficiency may exhibit other neurological symptoms, including:

• Abnormal muscle tone


• Weakness


• Tremors


• Ataxia (lack of coordination)


• Spasticity


• Delayed motor skills

5. Respiratory Distress: Some individuals with NAGS deficiency may experience respiratory difficulties, such as rapid breathing or shortness of breath.

6. Liver Dysfunction: NAGS deficiency can also affect liver function, leading to hepatomegaly (enlarged liver), jaundice (yellowing of the skin and eyes), and abnormal liver enzyme levels.

7. Metabolic Acidosis: The accumulation of ammonia in the body can disrupt the acid-base balance, resulting in metabolic acidosis. This condition can cause symptoms such as rapid breathing, fatigue, and confusion.

Early diagnosis and treatment of N-Acetylglutamate Synthetase Deficiency are crucial to prevent complications and manage symptoms. Treatment typically involves a low-protein diet, medications to reduce ammonia levels, and in some cases, supplementation with N-carbamylglutamate, a synthetic form of N-acetylglutamate. Regular monitoring and close medical supervision are essential to ensure optimal management of the condition and prevent long-term complications.