Urea Cycle Disorder

What is the urea cycle?

The urea cycle is a filtering process to remove toxic substances from your body and keep other substances that are good for you moving throughout your body.

Urea (carbamide) is a substance made by your liver. The urea cycle begins when you eat. Your body breaks down (metabolizes) protein that comes from food in your diet and turns it into amino acids, which are the building blocks of proteins. Amino acids help your body build muscle, transport nutrients and keep your organs functioning. Digestion of proteins leads to waste products that turn into ammonia. Ammonia is toxic to your body. To remove ammonia, enzymes, which are proteins that produce chemical reactions, convert ammonia into urea. The following amino acids are in urea, along with ammonia:

• Arginine.
• Ornithine.
• Citrulline.

Enzymes move urea through your blood and kidneys. The final step of the urea process is to pass (excrete) urea from your body in your pee (urine).

What is urea cycle disorder?

Urea cycle disorder is a group of conditions where the process that moves urea through your body isn’t working as it should. It’s usually the result of a missing protein or enzyme. Urea cycle disorder is a genetic condition, also known as an inborn error of metabolism that causes ammonia to build up in your blood (hyperammonemia), which is toxic to your body. Symptoms of this condition target your brain and organ function.

What are the types of urea cycle disorders?

There are eight types of urea cycle disorders identified by the lack or malfunction (deficiency) of certain enzymes and proteins in your metabolism that process urea:

• N-acetylglutamate synthase (NAGS) deficiency.
• Carbamoylphosphate synthetase I (CPS1) deficiency.
• Ornithine transcarbamylase (OTC) deficiency.
• Argininosuccinate synthase 1 (ASS1) deficiency or Citrullinemia type I.
• Citrin deficiency or Citrullinemia type II.
• Argininosuccinic lyase (ASL) deficiency.
• Arginase (ARG) deficiency.
• Ornithine translocase deficiency.

Who does urea cycle disorder affect?

Urea cycle disorder can affect anyone since it’s a genetic condition. Newborns can receive a diagnosis a couple of days after they’re born through universal newborn screening blood tests. Sometimes symptoms aren’t noticeable until later in life and an adult can receive a diagnosis when symptoms become apparent.

Can I inherit urea cycle disorder?

Yes, urea cycle disorder is an inherited condition. Both of your parents need to pass a genetic mutation during fetal development for you to receive a diagnosis (autosomal recessive). Some types of urea cycle disorder pass onto children by attaching to a sex chromosome (X-linked) after conception.

How common is urea cycle disorder?

Urea cycle disorder affects 1 in 35,000 people in the United States.

What are the signs and symptoms of urea cycle disorder?

Early signs of urea cycle disorder are usually present soon after your baby is born but could happen at any age. Signs of urea cycle disorder include:

• Lethargy or feeling tired.
• Fussiness in babies.
• Nausea or vomiting.
• Can’t eat or feed.
• Breathing too fast or too slow.
• Confusion.

Symptoms of urea cycle disorder are the result of having too much ammonia in your blood (hyperammonemia). Symptoms range from mild to severe and could include:

• Problems with cognitive development and intellectual challenges.
• Behavioral changes.
• Developmental delays.
• The buildup of fluid around your brain (cerebral edema).
• Tight muscles (spasticity).
• Seizures.
• Coma.

Symptoms that affect your brain can be life-threatening.

What causes urea cycle disorder?

A genetic mutation causes urea cycle disorder. There’s a different genetic mutation that causes each type including:

• N-acetylglutamate synthase caused by a NAGS gene mutation.
• Carbamoylphosphate synthetase I caused by a CPS1 gene mutation.
• Ornithine transcarbamylase caused by an OTC gene mutation.
• Argininosuccinate synthase 1 caused by an ASS1 gene mutation.
• Citrin deficiency caused by an SLC25A13 gene mutation.
• Argininosuccinic lyase caused by an ASL gene mutation.
• Arginase caused by an ARG gene mutation.
• Ornithine translocase caused by an SLC25A15 gene mutation.

These genes are responsible for producing proteins and enzymes that move urea through your body. A genetic mutation causes your body to not produce enough of the proteins or enzymes that your body needs to function. If you have a type of urea cycle disorder, your body isn’t able to remove toxic ammonia from your body, where it collects in your blood and causes symptoms.

How is urea cycle disorder diagnosed?

Your provider will diagnose urea cycle disorder after a physical exam to review your symptoms and take a complete medical history. They might order a blood or urine test to confirm a diagnosis.

What tests to diagnose urea cycle disorder?

Tests to diagnose urea cycle disorder include:

• Amino acid profile or analysis: Your provider will test a small sample of your blood or urine to measure the amino acids that your body processes (metabolizes).
• Liver biopsy: Your provider will remove a very small piece of your liver to examine it under a microscope to look for enzymes associated with the condition.
• Genetic test: Your provider will examine a small sample of your blood to look for genetic changes that cause your symptoms.

How is urea cycle disorder treated?

Treatment for urea cycle disorder focuses on lowering the amount of ammonia in your blood, which could include:

• Eating a diet low in protein.
• Dialysis to clean your blood of toxins (hemodialysis).
• Taking medicine that includes sodium phenylacetate and sodium benzoate (Ammonul ®) to remove ammonia from your blood.
• Taking amino acid supplements (arginine or citrulline) to encourage your body to complete the urea cycle.

Severe cases of hyperammonemia could lead to a liver transplant.

Before starting treatment, talk to your provider about the possible side effects of new medication and procedures. Also, talk to your provider about any medicines or supplements you currently take to avoid drug interactions.

What foods should I avoid if I have urea cycle disorder?

Eating a diet low in protein is best to help you manage urea cycle disorder. When your body breaks down (metabolizes) protein in foods you eat, it converts the protein into amino acids, which continue to convert into ammonia. If you have urea cycle disorder, your body isn’t able to naturally remove ammonia from your blood. If you eat a diet low in protein, you reduce your risk of building up ammonia in your blood.

Some of the most common foods that contain protein that you should limit in your diet include:

• Fish.
• Chicken.
• Eggs.
• Beef.
• Beans.
• Tofu or soy-based foods.

Since protein is an essential part of your diet, removing all protein from your diet could cause side effects like limiting your growth. Your provider might suggest you work closely with a dietitian or nutritionist to help you manage your diet to limit the amount of protein you eat. Sometimes your provider will recommend taking vitamins, minerals or amino acid supplements to make up for a limited protein intake.

Can I breastfeed my newborn diagnosed with urea cycle disorder?

Your newborn receives protein from your chest milk (breastmilk). While it’s possible to chest feed your child, your provider will closely monitor how it affects your newborn. If your baby needs to reduce their protein intake, your provider might recommend using specialized infant formula instead of human milk.

How can I prevent urea cycle disorder?

You can’t prevent urea cycle disorder since it’s a genetic condition. If you plan on becoming pregnant and want to understand the risks of having a child with a genetic condition, talk to your provider about genetic testing.

What can I expect if I have urea cycle disorder?

Treatment will begin immediately if your provider diagnoses you with urea cycle disorder to reduce the amount of ammonia in your blood. Newborns diagnosed with the condition will receive immediate treatment after birth to prevent complications. Once treatment begins, your provider will check your blood ammonia levels until your blood ammonia reaches a safe level.

Your condition will need lifelong monitoring and a special diet that is low in protein. Eating too much protein can trigger your symptoms.

Severe cases of hyperammonemia can cause irreversible brain damage, which leads to coma or death. Talk to your provider about how you can manage your condition or your newborn’s condition to avoid these life-threatening complications.

What’s the prognosis for urea cycle disorder?

Your outlook depends on the severity of your symptoms. If you receive an early diagnosis with treatment and lifelong management, your life expectancy could be normal. If the condition is untreated or undiagnosed, it could be fatal.

When should I see my healthcare provider?

Visit your provider if you have symptoms of the condition, especially if you’re extremely tired or unable to eat.

It’s important to monitor your child’s developmental milestones as they grow to make sure they’re meeting expectations for their age. If your child doesn’t meet their developmental milestones, visit your healthcare provider.

Visit the emergency room if you or your newborn has a seizure or has trouble breathing.

What questions should I ask my doctor?

• How do I manage my child’s condition?
• Do I need to visit a nutritionist?
• What are the side effects of the treatment?
• What foods should I avoid?

A note from Cleveland Clinic

It may be overwhelming to learn that you or your newborn has a rare genetic condition. Your provider will help you manage your baby’s diagnosis or your diagnosis if you experience symptoms as an adult. Eating a diet low in protein reduces the way that the condition affects your body, which could minimize your symptoms so you can feel better. If you feel tired all the time, have trouble eating or experience changes to your behavior that aren’t normal, visit your provider.