Ornithine transcarbamylase is an enzyme that protects your body from the buildup of toxic ammonia. Your body makes ammonia when it breaks down protein. If you don’t have this enzyme, ammonia can build up in your blood and damage your brain. This condition is extremely treatable thanks to medical advances, especially within the last 25 years.
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OTC deficiency is when your liver can’t make enough of an enzyme called ornithine transcarbamylase (OTC). OTC is key for removing ammonia from your blood. OTC deficiency is serious, but very treatable.
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OTC deficiency is a type of urea cycle disorder. When you eat protein, bacteria in your intestines break it down and make ammonia as a waste product. Your liver uses a process called the urea cycle to turn ammonia into urea, and a key part of that process is OTC. Your kidneys filter the urea out of your blood and turn it into pee (urine) so your body can get rid of it.
OTC deficiency has three types:
OTC deficiency is rare overall, but it’s the most common urea cycle disorder. Researchers estimate it affects anywhere between 1 in 14,000 and 1 in 80,000 people. This condition is more common and more severe in males.
The symptoms of OTC deficiency depend partly on when it first develops. Symptoms are usually much more severe with the neonatal form. The symptoms are also much more likely to appear after consuming protein.
Neonatal symptoms include:
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Children between 1 month and 16 years old can have the same symptoms as newborns, plus the following:
Adult symptoms can include any of the same symptoms as in newborns and children, plus the following:
OTC deficiency is a genetic disorder, meaning it happens because of DNA changes. Researchers know of at least 400 different DNA changes that can cause this condition. But about 1 in 5 cases don’t have a DNA change that tests can detect.
There are two ways that these DNA changes can happen:
Inherited OTC deficiency is an X-linked condition. That means females are carriers and don’t have the full condition, but they can still have symptoms. Research shows that between 10% and 20% of female carriers develop symptoms at some point.
OTC deficiency can lead to high ammonia levels. High blood ammonia levels (hyperammonemia) poison your brain, causing metabolic encephalopathy. When that’s severe and/or lasts longer, it can cause the following complications:
Complications are more likely — and often more severe — with the neonatal type of OTC deficiency. They include:
OTC deficiency can also be very dangerous when you’re pregnant. But it’s possible to manage OTC deficiency during pregnancy and have a healthy baby. If you have OTC deficiency or a family history of it, it’s a good idea to talk to your Ob/Gyn. They can coordinate your care with the provider(s) you see about your OTC deficiency.
Diagnosing OTC deficiency mainly relies on lab tests, especially blood tests and urine tests. In many cases, it’s possible to diagnose it before birth using DNA tests. But while OTC deficiency is a genetic disease, DNA tests can’t always catch it. That’s because dozens of DNA changes can cause it.
Depending on where you live, there might be laws or regulations that require testing every newborn for OTC. In those places, OTC is much more likely to get an early diagnosis.
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In places that don’t have standard screenings, it can be difficult even for experienced providers to catch this disease after birth. That’s because the symptoms are very vague early on and can look like any number of conditions. In the most severe cases, brain damage from ammonia toxicity happens before providers can diagnose the condition.
OTC deficiency is very treatable. There are a few key parts to treating it:
In cases where providers diagnose OTC deficiency before birth, it might be possible to start treating the fetus. Providers can give alternative pathway drugs to the mother shortly before birth. That can keep the baby’s ammonia at a safe level after they’re born.
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Yes, there’s a way to cure OTC deficiency. A liver transplant can replace your liver with a healthy liver that can make OTC. Once transplanted, you can have a regular, nutritious eating plan and won’t need to take medications to lower ammonia.
Unfortunately, for several reasons, liver transplants aren’t common for this condition. Also, liver transplant recipients need lifelong care with immunosuppressants to avoid organ rejection. Your healthcare provider can tell you more about liver transplantation and how it would affect you.
Gene therapy trials for OTC deficiency are ongoing. This treatment could one day offer a non-transplant treatment option for people with OTC deficiency.
There’s no way to prevent OTC deficiency. But you can receive genetic counseling before you have biological children. This can’t prevent the disease, but it can help you understand the odds of your children inheriting it.
What you can expect with OTC deficiency varies depending on how severe your case is. The more severe your case, the less protein you can safely consume. Many people with OTC deficiency often follow a vegetarian diet before diagnosis because it’s what they prefer. Your healthcare provider can help determine how much protein you can consume and then guide you on how to monitor your intake.
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Overall, having OTC deficiency does affect your life in significant ways. High blood ammonia levels increase your risk of developing complications like intellectual disability. That’s one reason why keeping blood ammonia levels low is so important.
But overall, OTC deficiency is very manageable with monitoring, treatment and a low-protein diet. Monitoring your blood ammonia levels is crucial to keep them from getting too high. And if your blood ammonia levels increase, treatment can lower them.
OTC deficiency is congenital (meaning you have it at birth) and lifelong. A liver transplant is the only way to cure it.
The outlook for OTC deficiency depends mainly on when you start having symptoms. Research from 2020 shows the outlook for intermediate and adult cases is best. The death rate for them ranges from 8% to 13%.
Neonatal cases are usually the most severe and have the highest death rate. But that death rate is much lower than in years past. A 30-year study from 1971 to 2011 found that neonatal cases had a death rate of 74%. But a later study from 2001 to 2013 found that neonatal cases had a death rate of 43%.
You should go to the hospital or emergency room right away if you notice symptoms of high blood ammonia levels in yourself or your child. The longer that blood ammonia levels remain high, the greater the odds of having permanent brain damage.
Some questions you may want to ask your provider include:
Whether they affect you or your child, receiving a diagnosis of a lifelong genetic disease can make you feel a number of emotions. You might feel scared, anxious or angry, and those feelings are all understandable. But you should try to remember that OTC deficiency isn’t your fault, and it mainly happens for reasons you can’t control.
While OTC deficiency is serious, medical advances mean this condition is much more treatable than it was just a couple of decades ago. This condition is often manageable with regular monitoring and treatment. And there’s growing evidence backing liver transplants to cure this condition. If you have questions or need support along the way, don’t forget to lean on your healthcare team. Whether it’s to guide or support you, they’ll be there to have your back along the way.
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Last reviewed on 04/29/2025.
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