A urea cycle disorder is a genetic disorder that results in a deficiency of one of the six enzymes in the urea cycle. These enzymes are responsible for removing ammonia from the blood stream.
Male Urinary System
Image by TheVisualMD
What Is
Urea Nitrogen Molecule
Image by TheVisualMD
Urea Nitrogen Molecule
The blood urea nitrogen (BUN) test measures the amount of the waste urea found in the blood. Nitrogen, in the form of ammonia, is produced by the breakdown of proteins; it combines with carbon, hydrogen and oxygen to form urea, which is then released into the bloodstream and carried to the kidneys, where it is filtered out and eliminated in the urine. If the kidneys are damaged, their ability to remove urea from the blood is impaired.
Image by TheVisualMD
What Is a Urea Cycle Disorder?
A urea cycle disorder results from an inability to safely dispose of nitrogen in the body. When our bodies break down protein, we create nitrogen that is used for many chemical reactions in the body for growth, and excess nitrogen is made into a nontoxic chemical called urea that we get rid of through our urine.
But when that process goes wrong, in people with urea cycle disorders, the excess nitrogen is not flushed out through our urine. Instead, the nitrogen builds up as ammonia in our bodies and causes damage, particularly in the brain.
Source: NIH MedlinePlus Magazine
Additional Materials (11)
Detoxification of Ammonia in the human body
Video by 5MinuteSchool/YouTube
Male Urinary System
This anterior view of a male torso reveals the upper urinary tract (kidneys, ureter and bladder) in situ. Anatomy overlaying this system including the liver, pancreas, small intestines, and ribs, have been \"ghosted in\" in order to allow an unobstructed view of the structures underneath. Completely visible anatomy surrounding the kidneys include the perirenal fat, adrenal gland, pelvis, aorta, vena cava and lower spinal column. The kidneys are the body's primary filtering system, responsible for processing and eliminating wastes from the bloodstream such as excess salts and proteins. Once extracted, these are then broken down into a substance called urea. Urea flows to the bladder and is eventually expelled as urine. Working non-stop day and night, the kidneys filter nearly 200 quarts of blood per day, producing about two quarts of urine (depending on body size). The left kidney is usually positioned slightly higher in the body than the right. This occurs because the developing liver on the right side of the spine grows more rapidly than the kidneys and displaces the right kidney downwards.
Image by TheVisualMD
The Basics of Inborn Errors of Metabolism | Webinar | Ambry Genetics
Video by Ambry Genetics/YouTube
Urea Cycle Disorders
Video by childrenshospgh/YouTube
Urea Cycle Disorders
Video by Mount Sinai Health System/YouTube
Behind the Mystery: Urea Cycle Disorders
Video by The Balancing Act/YouTube
Metabolism | Urea Cycle
Video by Ninja Nerd/YouTube
Disorders of the Urea Cycle - CRASH! Medical Review Series
Video by Paul Bolin, M.D./YouTube
Ask Hermin: Urea Cycle Disorder
Video by The SKOOP at SickKids/YouTube
Urea cycle TRICK to MEMORIZE - HOW TO REMEMBER UREA CYCLE FOREVER
Video by MEDSimplified/YouTube
Urea Cycle Made Simple - Biochemistry Video
Video by MEDSimplified/YouTube
3:32
Detoxification of Ammonia in the human body
5MinuteSchool/YouTube
Male Urinary System
TheVisualMD
51:59
The Basics of Inborn Errors of Metabolism | Webinar | Ambry Genetics
Ambry Genetics/YouTube
1:09
Urea Cycle Disorders
childrenshospgh/YouTube
7:03
Urea Cycle Disorders
Mount Sinai Health System/YouTube
7:47
Behind the Mystery: Urea Cycle Disorders
The Balancing Act/YouTube
19:16
Metabolism | Urea Cycle
Ninja Nerd/YouTube
17:24
Disorders of the Urea Cycle - CRASH! Medical Review Series
Paul Bolin, M.D./YouTube
3:32
Ask Hermin: Urea Cycle Disorder
The SKOOP at SickKids/YouTube
5:52
Urea cycle TRICK to MEMORIZE - HOW TO REMEMBER UREA CYCLE FOREVER
MEDSimplified/YouTube
2:49
Urea Cycle Made Simple - Biochemistry Video
MEDSimplified/YouTube
Is It Common?
Health Statistics
Image by geralt/Pixabay
Health Statistics
Image by geralt/Pixabay
How Many Patients Have a Urea Cycle Disorder?
We think that it's about 1 in 30,000. We don't know the exact number of patients out there because many individuals remain undiagnosed or have very mild symptoms, especially adults.
Source: Genetic and Rare Diseases Information Center (GARD)
Causes
Genetics
Image by Pixabay
Genetics
Genetics
Image by Pixabay
How Do People Get Urea Cycle Disorder?
Urea cycle disorders are genetic conditions. They can arise from inheriting a mutated gene from the parents or it may start as a new condition in the patient.
Source: CNX OpenStax
Testing
Ammonia Levels
Also called: Ammonia, NH3, Hyperammonemia Test
An ammonia levels test measures the amount of ammonia (NH3) in your blood. High ammonia levels can cause serious brain damage and coma.
Ammonia Levels
Also called: Ammonia, NH3, Hyperammonemia Test
An ammonia levels test measures the amount of ammonia (NH3) in your blood. High ammonia levels can cause serious brain damage and coma.
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Use the slider below to see how your results affect your
health.
μg/dL
27
102
Your result is Normal.
A normal ammonia level may mean that your signs and symptoms are due to a cause other than excess ammonia. However, normal levels of ammonia do not rule out hepatic encephalopathy.
Related conditions
An ammonia levels test measures the amount of ammonia in a sample of your blood. Ammonia is also called NH3. It is a normal waste product in your body. Healthy bacteria in your intestines make ammonia when you digest protein in the foods you eat.
Normally, your liver changes ammonia into another waste product called urea. Your kidneys get rid of urea in urine (pee). This process is called the urea cycle.
When you're healthy, the urea cycle prevents ammonia from building up in your blood. This is very important because ammonia is toxic (poisonous) to your brain. Even small increases in the level of ammonia in your blood can cause permanent brain damage, coma, and even death.
Liver disease is the most common cause of high ammonia levels. Other causes include kidney failure and genetic disorders called urea cycle disorders.
The medical term for high ammonia levels is hyperammonemia.
An ammonia levels test may be used to help diagnose high ammonia levels in people who have symptoms. The test alone can't diagnose conditions that increase the amount of ammonia in your blood. But it may be used with other tests to help find the cause.
Ammonia levels testing can help diagnose conditions such as:
Hepatic encephalopathy. This condition happens when toxins (poisons), including ammonia, build up in your brain because your liver is unable to break them down. It can cause memory loss, confusion, loss of consciousness, and coma.
Reye syndrome. This rare disease damages the brain and liver. Without treatment, it causes death. It mostly happens in children younger than 15 who have had a viral infection that causes a fever, such as chickenpox or the flu. Taking aspirin during a viral illness may increase the risk of Reye syndrome.
Urea cycle disorders (UCDs). This is a group of rare genetic conditions that you inherit from your parents. If you have a UCD, you lack enzymes that help change ammonia into urea. An enzyme is a protein that speeds up certain chemical reactions in your body. Symptoms may show up shortly after birth or later in life. Newborns are tested for certain UCDs as part of routine newborn screening. Your child's health care provider can explain more about which UCD screening tests are used in your state.
Ammonia levels testing is also used to monitor conditions that cause high ammonia levels and to check if treatment is working.
You may need this test if you have symptoms that could be from too much ammonia in your blood. The symptoms depend on how high your ammonia levels are and your age. Symptoms in children and adults may include:
Feeling irritable
Lack of energy and mental alertness or being very sleepy
Vomiting
Headache
Loss of muscle coordination that may cause difficulties with walking or speech
Changes in behavior
Confusion, including not being sure about the time and/or where or who you are
Mood swings
Seizures
Other symptoms in children may include:
Not growing taller or gaining weight as expected
Lack of muscle tone (limp muscles)
Developmental delays in children or infants
Newborn babies may develop symptoms of high ammonia levels within three days after birth. Symptoms in newborns include the above symptoms and may also include fast breathing and/or making grunting sounds when breathing. If your baby or child has any symptoms of high ammonia levels, contact their provider right away.
If you have a family history of genetic urea cycle disorders, you or your child may need this test even if you don't have symptoms.
If you've been diagnosed with high ammonia levels, you may need this test to see how well your treatment is working.
In most cases, a health care professional will take a blood sample from a vein in your arm, using a small needle. After the needle is inserted, a small amount of blood will be collected into a test tube or vial. You may feel a little sting when the needle goes in or out. This usually takes less than five minutes.
In certain cases, the blood sample may be taken from an artery, which is a blood vessel that carries blood from your heart to the rest of your body. Some providers think blood from an artery may provide more accurate results. The blood is taken from an artery in your wrist, arm, or groin using a needle attached to a syringe.
Taking blood from an artery tends to be more uncomfortable than blood tests that use a vein. So, numbing medicine may be applied to your skin first. Afterwards, the site will be bandaged, and pressure will be applied for at least five minutes to stop bleeding. You may be told to avoid lifting heavy objects for 24 hours after the test.
To get a blood sample from a newborn, a provider will clean the baby's heel with alcohol. Then the provider will stick the baby's heel with a small needle to collect a few drops of blood. The heel will then be bandaged.
Your provider will give you specific instructions about how to prepare for an ammonia levels test. You should not smoke for several hours before the test. You may be asked to avoid strenuous exercise and alcohol for a period of time.
You may also need to fast (not eat or drink) for several hours. Your provider may tell you to stop taking certain medicines, including diuretics (water pills) and opioid pain medicines. But never stop taking any prescription medicines without talking with your provider first.
Babies do not need any special preparations before the test.
There is very little risk to having a blood test. You may have slight pain or bruising at the spot where the needle was put in, but most symptoms go away quickly.
If your blood sample was taken from an artery, you may also have some bleeding where the needle was put in. Very rarely, the needle may damage a nerve or the artery.
Your provider will use your test results, symptoms, and medical history to understand what your ammonia levels say about your health. Normal levels vary with age, but in general, low levels are normal and healthy.
If your test results are normal, your provider will order other tests to find out what's causing your symptoms.
If your test results show ammonia levels that are higher than normal, it usually means that your body is having trouble getting rid of ammonia. Many types of health conditions can cause high ammonia levels, including:
Liver diseases, such as cirrhosis or hepatitis
Hepatic encephalopathy
Kidney disease or kidney failure
Certain genetic disorders, including urea cycle disorders
Reye syndrome (most common in in children and teens)
Taking certain medicines
If the results of an ammonia levels test are high, more tests will usually be done to diagnose the cause. Treatment will depend on the condition that's causing the problem. If you have questions about your test results or treatment, talk with your provider.
Ammonia Levels: MedlinePlus Medical Test [accessed on Jan 18, 2024]
Ammonia blood test: MedlinePlus Medical Encyclopedia [accessed on Mar 15, 2019]
Ammonia - Health Encyclopedia - University of Rochester Medical Center [accessed on Mar 15, 2019]
Ammonia Test - Testing.com. Mar 18, 2022 [accessed on Jan 18, 2024]
Normal reference ranges can vary depending on the laboratory and the method used for testing. You must use the range supplied by the laboratory that performed your test to evaluate whether your results are "within normal limits."
Additional Materials (5)
Symptoms of hyperammonemia
Main symptoms of hyperammonemia (See Wikipedia:Ammonia#Ammonia's role in biological systems and human disease).
To discuss image, please see Template talk:Human body diagrams
Image by Mikael Häggström.
When using this image in external works, it may be cited as:
Häggström, Mikael (2014). "Medical gallery of Mikael Häggström 2014". WikiJournal of Medicine 1 (2). DOI:10.15347/wjm/2014.008. ISSN 2002-4436. Public Domain.or
By Mikael Häggström, used with permission./Wikimedia
Ammonia, Urine
Ammonia is a waste product generated by intestinal bacteria during the digestion of protein. From the intestine, ammonia is transported to the liver, where it is converted into urea, which is then excreted in the urine by the kidneys. The conversion and elimination of ammonia can be impaired by liver disease or kidney damage, which can result in a dangerous build up of ammonia.
Image by TheVisualMD
Ammonia, Hypertension
Ammonia is a waste product generated by intestinal bacteria during the digestion of protein. From the intestine, ammonia is transported to the liver, where it is converted into urea, which is then excreted in the urine by the kidneys. The conversion and elimination of ammonia can be impaired by liver disease or kidney damage, which can result in a dangerous build up of ammonia. Lower-than-normal levels of ammonia may be seen with some times of hypertension.
Image by TheVisualMD
Blood Urea Nitrogen (BUN): Protein
Nitrogen, in the form of ammonia, is produced by the breakdown of proteins; it combines with carbon, hydrogen and oxygen to form urea, which is released into the blood; the kidneys, in turn, filter it out and eliminate it in the urine.
Image by TheVisualMD
Ammonia molecule, NH3
A van der Waals' surface coloured according to charge, superimposed on a ball-and-stick model of the ammonia molecule, NH3. Red represents partially negatively charged regions, blue represents partially positively charged regions, and white represents neutral (uncharged) regions.
Image by Ben Mills
Symptoms of hyperammonemia
Mikael Häggström.
When using this image in external works, it may be cited as:
Häggström, Mikael (2014). "Medical gallery of Mikael Häggström 2014". WikiJournal of Medicine 1 (2). DOI:10.15347/wjm/2014.008. ISSN 2002-4436. Public Domain.or
By Mikael Häggström, used with permission./Wikimedia
Ammonia, Urine
TheVisualMD
Ammonia, Hypertension
TheVisualMD
Blood Urea Nitrogen (BUN): Protein
TheVisualMD
Ammonia molecule, NH3
Ben Mills
Zoey's Story
Zoey’s Story: One Family’s Experience with a Rare Disease
Undiagnosed urea cycle disorder takes life of college student
Zoey Zalusky, right, was 19 years old when she passed away suddenly from a rare disease. Image credit: Renee Zalusky
In 2015, college student Zoey Zalusky was 19 years old with an exciting future ahead of her. She had a supportive, loving family, and a close circle of friends. She was studying to be a nurse and getting good grades at the University of Arizona at Tucson.
"She was our social butterfly," says Renee Zalusky, Zoey's mom. "She was always everywhere and wanting to do everything. She had a lot of energy." Zoey was the middle of three children.
But in December of that year, everything changed. Zoey suddenly passed away from an undiagnosed, rare genetic condition: ornithine transcarbamylase deficiency (OTC), which is part of a larger group of urea cycle disorders.
The disorder can go unnoticed for years, as it did in Zoey's case. If not diagnosed, it can lead to a buildup of toxic levels of ammonia in the body, which can cause brain damage and other serious complications. Ammonia builds up because people with the disorder cannot dispose of excess nitrogen—which comes from the protein we eat and the protein in our muscles—through their urine.
Zoey's childhood
Renee says looking back there were some symptoms, but they didn't seem out of the ordinary at the time. In general, Zoey was a healthy, happy child.
"As far as health goes, I always described her as energetic and full of life," Renee says. "Whenever we'd go to her annual check up, there were never any problems." Zoey played sports growing up and swam on the varsity swim team in high school.
But Zoey did have an aversion to protein from the time she was little and always preferred carbohydrates and salads. With urea cycle disorder, people often avoid protein because it can make them feel sick. In Zoey's case, it just seemed like something a lot of kids do: picky eating.
"Zoey never ate a burger in her life. She never ate a steak," Renee says. "It's easy to see now that she had a definite aversion to protein because it probably made her feel sick."
As she got closer to adolescence, Zoey started to have uncontrolled episodes of vomiting. It only happened once in a while, with no warning, sometimes during high stress periods, Renee says.
"She would just out of the blue suddenly vomit. Sometimes she knew it was going to happen and sometimes she wouldn't," Renee says.
Her health care providers at the time thought it might be food allergies or sensitivities. They suggested eliminating certain food groups and then re-introducing them slowly, to see if they could determine what was causing her nausea and vomiting.
Overall, they did not seem concerned about the situation and Zoey never really took the diet modifications seriously.
2015
Zoey's disease went unnoticed until the winter of 2015.
It was the first semester of her sophomore year, and Zoey didn't feel well. She called her mom (who lives in Texas) saying she fell asleep at 4 p.m. the day before and had slept until 9:00 a.m. the next morning. Her words were jumbled and she wasn't making sense. "She was so upset because she was trying to tell me she had missed an assignment the day before," Renee says. "At first I thought she might have been drinking."
Hours later, Zoey wound up in the emergency room at the college's hospital. Her doctors considered alcohol poisoning, but after doing a variety of tests, including drug and alcohol screening, they weren't able to diagnose anything in particular.
Looking back, Zoey was having a reaction to the ammonia buildup in her body due to urea cycle disorder.
"They came to the conclusion that she was mildly dehydrated," Renee says. "The only thing that really raised some red flags were that her liver enzymes were slightly elevated."
The doctors gave her fluids, which seemed to help. Zoey was told to come back a few days later for a checkup and to follow up with her family doctor.
Zoey had a few repeat blood tests, which showed her liver enzymes were still high. But overall, she seemed back to normal and tried to catch up on schoolwork, Renee says.
But a few weeks later, Zoey collapsed. Her urea cycle disorder caused her to have irreversible brain damage due to the high levels of ammonia in her body, which led to a fatal coma.
Discovering urea cycle disorder
After Zoey passed away, her parents made the decision to donate her organs. On Christmas Day 2015, three people received the gift of lifesaving organs. This is how they eventually discovered what led to Zoey's coma.
The Arizona Donor Network contacted them, letting them know that the man who received Zoey's liver had died shortly after due to complications from urea cycle disorder.
Zoey's whole family (her parents and two siblings) were all tested at Baylor College of Medicine in Houston after hearing this. They discovered that Zoey's father, John, also has OTC deficiency. The disease had developed spontaneously in utero, or before he was born.
Spreading the word
Zoey's family still works closely with doctors at Baylor, who help John manage his OTC deficiency. Baylor also helped connect them with the National Urea Cycle Disorders Foundation (NUCDF), a patient advocacy group. They're committed to telling Zoey's story to help others and share her memory. A special part of this was a video discussing Zoey's life and her OTC story.
"Zoey never ate a burger in her life. She never ate a steak. It's easy to see now that she had a definite aversion to protein because it probably made her feel sick."
-Renee Zalusky
Renee is also spreading the word about blood ammonia tests, which can help diagnose urea cycle disorders. Zoey's ammonia level was not tested during either of her hospital stays.
"It's not an expensive test to do, but it's not an easy one either," Renee says.
For an ammonia test, the blood sample must be run immediately, because after 30 minutes there is a risk of a false positive.
The NUCDF has created a website that seeks to address this lack of awareness among medical professionals about the hidden dangers of ammonia poisoning.
"It was so devastating for us that nobody had ever really heard of this disorder, and it became really important to tell people Zoey"s story," Renee says. "We've been trying to do whatever we can to support efforts to educate the public, as well as emergency room personnel. If even one family can be saved from what happened to us, it will be worth it."
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Urea Cycle Disorders
A urea cycle disorder is a genetic disorder that results in a deficiency of one of the six enzymes in the urea cycle. These enzymes are responsible for removing ammonia from the blood stream.