What is NAGS deficiency?

N-acetylglutamate synthase (NAGS) (pronounced “nag S”) deficiency is a genetic disorder that can be passed down among family members. This disorder blocks or limits your body’s ability to remove ammonia (a waste product produced by your body). This leads to excess ammonia building up in your blood. At high levels, ammonia is toxic (or poisonous), especially to your brain. If left untreated, high blood ammonia levels can lead to brain damage or even death.

Symptoms of NAGS deficiency can be treated. Learn more about this proven treatment for the symptoms of NAGS deficiency.

Any episode of acute hyperammonemia (high blood ammonia levels) with symptoms should be treated as a life-threatening emergency. Prompt use of all therapies necessary to lower blood ammonia levels is essential. This may require using a dialysis machine to remove ammonia.


NAGS deficiency and the urea cycle

NAGS deficiency is a disorder that blocks or limits your body’s ability to remove ammonia through a process called the urea cycle.

When your body breaks down proteins from the foods you eat, ammonia is produced as a waste product. Because excess ammonia is so toxic, your liver must change it into a less toxic substance—called urea—before it can be removed through your urine.

To start this process, your body needs a specific enzyme called NAGS.

When you have NAGS deficiency, your body either has too little NAGS enzyme activity or none at all or it makes NAGS that does not work properly. The job of NAGS is to produce the cofactor NAG, which is the key that starts the urea cycle. So, without NAGS, the urea cycle cannot start, and ammonia builds up in the blood.

Here’s how the urea cycle works in someone who does not have NAGS deficiency:

  1. The NAGS gene provides instructions for making an enzyme called NAGS.
  2. The job of the NAGS enzyme is to produce a cofactor called N-acetylglutamate, or NAG.
  3. NAG then acts like a key to activate (or “turn on”) an enzyme called CPS1. CPS1 initiates the first step in breaking down ammonia in the urea cycle.

NAGS deficiency is a genetic disorder― learn how it may affect your family members.

In order to have NAGS deficiency, you must have inherited two copies of the affected gene, one from each parent. People who have just one copy of the affected gene will not have NAGS deficiency.

If your child has been diagnosed with NAGS deficiency:

Talk to your child’s doctor about testing your other children. Each child has a 1 in 4 chance of having NAGS deficiency.

If you have been diagnosed with NAGS deficiency:

Talk to your siblings about your diagnosis. This is especially important if they have had unexplained symptoms that could have been caused by NAGS deficiency.

What are the symptoms of NAGS deficiency?

NAGS deficiency causes a wide range of symptoms. High blood ammonia levels result in most symptoms of NAGS deficiency being neurological (involving the brain). This is why these high ammonia levels in your blood are so dangerous.

Newborns (Neonates – Days 1-28)

Symptoms of NAGS deficiency may appear in the first few days of life. Common early symptoms in newborns include:

  • Poor feeding or poor appetite
  • Vomiting
  • Changes in body temperature
  • Muscle weakness
  • Drowsiness or sleepiness
  • Abnormal breathing
  • Seizures

As excess ammonia builds up, more severe symptoms can develop, like coma and even death. This can happen quickly. That’s why it’s important to never ignore these symptoms—even if they seem mild. Tell your baby’s doctor about any symptoms right away.

Infants, Children, & Adults

Some people with NAGS deficiency may not develop signs and symptoms until the first months of life—or even well into adulthood.

Symptoms that develop later in life vary widely. Severe symptoms may develop suddenly in someone who was previously healthy. Less severe symptoms may occur on and off over a period of years. This is known as chronic (happening for a long time) hyperammonemia or chronic ammonia toxicity.

Signs and symptoms in people with NAGS deficiency may include:

  • Abdominal pain, vomiting, loss of appetite, protein avoidance, low body weight, or failure to thrive
  • Fatigue or problems sleeping
  • Headaches or migraines
  • Vision disturbances
  • Tremor, uncontrolled movements, or poor coordination
  • Confusion or dizziness
  • Slurred or slow speech
  • Irritability
  • Hyperactive or aggressive behavior
  • Learning difficulties
  • Seizures
  • Coma

Never ignore these symptoms—even if they seem mild. Left untreated, any and all symptoms may get worse and can cause permanent brain damage, coma, or even death. Tell your or your child’s doctor about any symptoms right away.

What things may trigger symptoms?

Adding stress to the urea cycle process can cause the ammonia level in your blood to rise. Triggers to watch out for include:

  • Illness

  • Trauma

  • Internal bleeding

  • Surgery

  • Certain medications

  • Increase in dietary protein

    (such as during a barbecue)

  • Protein avoidance or starvation

  • Intense or lengthy physical exercise

  • Pregnancy

Symptoms of high blood ammonia levels due to NAGS deficiency can be treated. Learn more.

How is NAGS deficiency diagnosed?

If your doctor suspects you may have NAGS deficiency, he or she will order a series of laboratory tests:

1. First, your doctor will test your blood ammonia level. What is considered “normal” for a blood ammonia level varies based on your age. If your blood ammonia level is high for your age, this may be a sign of an inherited urea cycle disorder like NAGS deficiency. But there are also other causes for high blood ammonia levels.

2. If your blood ammonia level is high, your doctor will order more blood and urine tests. NAGS deficiency is one of a handful of urea cycle disorders caused by a missing or defective enzyme. These additional tests will measure the different chemicals in your body that are involved in or affected by the urea cycle, such as amino acids like glutamine and citrulline. The results may be helpful to determine which urea cycle disorder you may have.

Blood and urine tests must be done in a particular way and must be processed very quickly. Experienced laboratories know the procedures for handling samples and measuring and monitoring blood ammonia and other chemicals in your body.

A prompt, accurate diagnosis is critical because high blood ammonia levels are toxic to the brain.

DNA Testing

DNA testing is necessary to confirm a diagnosis of NAGS deficiency. DNA testing does not need to be done when symptoms are present. Family members of someone diagnosed with NAGS deficiency may want to talk to their doctors about getting tested.

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