A health condition that causes the body not to produce an enzyme that protects it from a buildup of toxic ammonia is called OTC deficiency. This enzyme is known as ornithine transcarbamylase, and it helps get rid of ammonia that appears when the body breaks down proteins. If this substance accumulates in the blood, it may cause damage to the brain. Fortunately, there are different options to treat this condition.
Normally, this enzyme is produced by the liver. OTC deficiency often occurs when the liver is no longer able to produce enough of this enzyme. Furthermore, this condition is a type of urea cycle disorder. Ammonia appears in the body when the bacteria in the intestines break down the protein. Generally, ammonia is a waste product that should be removed from the body.
However, this condition rarely affects people, but it is the most common urea cycle disorder. According to some data, OTC deficiency affects about 1 in 14,000 to 1 in 80,000 people.
Types of OTC Deficiency
Doctors have divided this condition into 3 categories. For example:
- Neonatal – This type of condition often appears within 30 days of life. Furthermore, it is the most severe form that can cause serious and even life-threatening complications.
- Intermediate – It usually occurs between the ages of 1 month and 16 years.
- Late – In such cases, OTC deficiency appears after age 16, but it may occur after age 60. The late form of OTC deficiency is a mild form that often causes mild to moderate symptoms.
Symptoms
The symptoms may appear differently among people with this condition because it depends on when it first develops. Usually, people experience symptoms when they eat protein. Check below the symptoms of this condition according to the type:
Neonatal Symptoms
- Vomiting
- Lethargy
- Irritability
- Appetite changes
- Muscle weakness (hypotonia)
- Hepatomegaly (enlarged liver)
- Seizures
Intermediate Symptoms
Usually, children with this type of OTC deficiency experience some of the previous symptoms and the following ones. For example:
- Ataxia (loss of coordination)
- Delirium
- Confusion
Late Symptoms
While the late form of OTC deficiency is the mildest form, it still can cause serious symptoms in some people. Check below some examples:
- Hallucinations
- Dysarthria (speaking problems)
- Migraines
- Nausea
- Vision changes (such as blurred vision, double vision, and others)
Immediately contact your healthcare professional if any of the previous symptoms appear.
Causes
This condition is a genetic disorder that occurs due to a DNA mutation (change). Experts have found more than 400 DNA mutations that may cause OTC deficiency. However, 1 in 5 cases do not have a DNA mutation that tests can identify. These gene changes can occur in two ways. For example:
- Inherited – In such cases, the abnormal genes are passed from biological parents to their children during pregnancy. Commonly, males who have the abnormal gene develop the condition, but females who get the mutated genes often become carriers. It is true for about 36% to 80% of OTC deficiency cases.
- Noninherited – Sometimes, babies do not inherit the abnormal genes from their biological parents. However, if they have this condition, the abnormal gene has occurred randomly during fetal development.
The inherited form of this condition is an X-linked disorder. That’s why women do not develop it fully. According to some research, females with the abnormal genes that cause OTC deficiency can experience some symptoms at some point.
Risk Factors
Healthcare professionals have also identified some factors that may increase your risk of developing this condition. Check below some examples:
- Infection or fever – Some health problems may increase metabolic demand, which significantly increases the ammonia levels.
- Surgery – Surgical procedures (particularly bariatric surgery) may cause a crisis.
- Fasting – People who do not eat food for a long period are also at increased risk of developing OTC deficiency.
- High-protein intake – Those who eat a high-protein diet or total parenteral nutrition (TPN) are at increased risk of a hyperammonemic episode.
- Pregnancy
Complications
This condition can significantly increase the levels of ammonia in the blood, causing hyperammonemia. It often causes poisoning of your brain (metabolic encephalopathy). Usually, babies with the neonatal form of the condition experience the most severe complications. Check below some examples:
- Intellectual disability
- Developmental delays
- Coma
- Cerebral palsy
- Death
This genetic condition becomes very dangerous if it occurs during pregnancy. However, there are multiple options to treat this condition. You can also talk with your physician about ways to reduce the risk of developing the previous complications.
How to Prevent OTC Deficiency?
Unfortunately, there is no way to prevent this condition because it is a genetic disorder. However, you can get genetic counseling before pregnancy. It is also recommended to perform a genetic test to make sure you do not have abnormal genes that may cause OTC deficiency. It is essential to understand the risks of having children with OTC deficiency.
Diagnosis
Usually, this condition is diagnosed based on laboratory tests, including blood and urine tests. Sometimes, physicians may diagnose OTC deficiency before pregnancy using a DNA test. However, this is a genetic disease that can be caused by multiple abnormal genes (more than 400). That’s why DNA tests cannot always catch them. Furthermore, in some countries may be laws that require testing every newborn for OTC. When there are no standard screenings is often difficult to diagnose this condition after birth.
Treatment
Check below some treatment options often recommended by doctors for people with OTC deficiency:
- Reducing blood ammonia levels – Dialysis is one way to get rid of excessive ammonia from the body. However, this treatment is often recommended in severe cases.
- Alternative pathways therapy – Doctors may also prescribe some medicines called nitrogen-scavenging agents that affect the process of ammonia formation. These include Sodium benzoate and Sodium Phenylacetate.
- Dietary changes – Physicians usually recommend reducing the protein intake if you have OTC deficiency. It helps maintain ammonia in the blood at safe levels.
- Regular monitoring – You should also perform regular blood tests to make sure ammonia levels are within a healthy range.
Frequently Asked Questions
Can OTC deficiency be cured?
The only way to cure this genetic disorder is a liver transplant. After this treatment, you should have a regular, nutritious plan and no longer administer medicines to reduce ammonia levels. However, liver transplants are not common for this disorder. Moreover, liver transplant recipients require lifelong immunosuppressants to avoid organ rejection. In addition, gene therapy trials for this condition are ongoing, and one day could be a non-transplant option to cure OTC deficiency.
How long does OTC deficiency last?
This is a genetic condition that lasts for the rest of your life once you get it. In other words, OTC deficiency is a congenital (present at birth) disorder.
What is the outlook for OTC deficiency?
The prognosis of this condition depends primarily on when you begin having symptoms. Furthermore, a study from 2020 showed that the prognosis for intermediate and late forms of OTC deficiency is good. In general, the death rate for these types ranges from 8% to 13%, but for neonatal OTC deficiency (the most severe type), the death rate ranges from 43% to 74%. If you have additional questions, ask your healthcare professional.
