Also known as OTC, Ornithine Transcarbamylase Deficiency is a rare inherited metabolic condition named for the enzyme that people with OTC are missing and is estimated to occur between 1 in 56,500 to 1 in 77,000 people.

But what does that mean?
Many foods contain protein. You may immediately think of the more obvious foods like chicken, but protein can also be present in other foods, like sweets and vegetables. The body needs protein for growth and repair. Many people eat more protein than they need and so the body removes the excess protein.

Unused protein first gets converted into a toxic chemical called ammonia. This chemical can cause damage to the body and brain if it’s not removed and is allowed to build up. Usually, our bodies remove the ammonia through a process known as:

The Urea Cycle
The Urea Cycle takes place in the liver. It converts ammonia to a non-toxic chemical called urea. Several steps have to take place within the cycle to achieve this and each step needs an enzyme (like chemical scissors) for it to work. Urea is then removed from the body by the kidneys, before it’s excreted as urine.

In OTC deficiency, the body lacks the enzyme ornithine transcarbamylase. This means the process above cannot happen. The liver cannot convert the waste protein into urea as fast as it usually would. This can lead to high levels of ammonia.

This build up in ammonia means some babies can become ill in the first few days of life, whilst some may be diagnosed later as children. For both, the effects of high ammonia, known as hyperammonaemia, can quickly become life-threatening if untreated.

Diagnosis and Management
Currently OTC deficiency is suspected in someone with high ammonia levels, which can be picked up through a blood test. Diagnosis is then confirmed by finding a mutation in the OTC gene.

OTC deficiency is managed with a protein restricted diet, regular feeding, and medications and supplements. It’s important to get the protein balance right! Too little and there’s not enough to grow, too much and waste protein will cause high ammonia levels. Some may need a feeding tube to help with this, or might consider a liver transplant if management isn’t sufficienct.

There is a focus on OTC deficiency within the clinical trial landscape at the moment. Many researchers and companies are showing interest in this rare condition, with active and upcoming clinical trials either to study new treatments or better understand the cause and effects of OTC.

Currently, OTC is managed through diet and medication, but this doesn’t address the root cause of the issues. Liver transplant is the only cure at this time, and whilst this can be an incredible improvement for many, it can come with risks and can sometimes be seen as resolving one thing that needs managing but replacing it with another. Anyone who’s undergone organ transplant needs to take drugs to suppress their own immune system and reduce the risks of the organ being rejected by the body. Where it is an option, the decision to go ahead with a liver transplant is therefore one that needs careful consideration.

But why OTC?

There’s no clearly cited reason for the current industry focus on OTC we’re seeing. Though there could be a few of reasons for this:

• Despite UCDs being rare, there is good understanding of the urea cycle itself.
• OTC is also the most common of the Urea Cycle Disorders.
• Like the other UCDs, treatment is focused solely around preventing the build-up of ammonia and the subsequent effects of this so it’s relatively easy to test and prove the how well a treatment works, with clear markers and symptoms that are easily identified and measured.
• How and where the enzymes of the urea cycle are located is vastly important, this solely being in the liver. A liver transplant therefore can be curative. Liver transplantation although largely positive is generally considered for those with more severe illness.
  
• Current treatments of diet and medication are burdensome and can be tricky to navigate and maintain.

We have received the information from companies with clinical trials focusing on the treatment of OTC deficiency. More work is being done by others, such as Ultragenyx and Moderna, and we will share this as soon as it is available to us. 

Each of the tiles below are clickable and will bring you to our webpage containing further information about the specific treatment you clicked on.

We hope this page has been helpful and has provided you with an insight into trial information for OTCd Although clinical trials must gain approvals and follow strict regulations and processes to ensure safety, all clinical trials carry some degree of risk.

If you do have an interest in participating in a clinical trial it is important you gather all information available. You can discuss this with your consultant or the lead investigator of a trial who’ll be happy to provide more information and help you make an informed decision without committing to participating.