Frequently Asked Questions

What is OTC Deficiency?

OTC (Ornithine Transcarbamylase) Deficiency is a rare, genetic condition that can impact infants, children and adults. It is a condition whereby the body does not produce enough of, or any OTC enzyme responsible for breaking down protein into urea through a process called urea cycle. This process happens mainly in the liver.

OTCD is an X-linked disorder. This means that only one parent needs to have the mutation to pass it on to their child. Affected women have a 50% chance of passing on a mutated OTC gene to their daughter and son. All men with an OTC gene mutation will pass the genetic error to their daughters, but not to their sons because boys have only one X chromosome (received from the mother) and one Y chromosome (received from the father).

The most severe form of OTCD is diagnosed during the first 28 days of life. This is referred to as ‘early onset.’ People diagnosed with ‘later onset’ OTCD are usually less severely impacted because they may have more enzymatic activity; however, that is not always the case. More research is surfacing to correlate specific mutations with disease severity, regardless of ‘early’ versus ‘later’ onset diagnosis.

Without receiving an accurate diagnosis and proper treatment, many individuals with this condition die. OTCD can also lead to coma and brain damage in both adults and children. This can happen rather quickly. Furthemore, individuals impacted by OTCD are at risk for seizures, developmental delays and movement disorders such as dystonia. With recurrent crisis episodes, this risk increases.

Some people with OTCD may never show any symptoms. This is mostly applicable to women, but not always, because they have two copies of the gene (correct and altered copy), one on each X chromosome. Over 500 different variants (genetic errors) have been identified in the OTC gene. Some studies have established a predictability model for specific OTC variants. This demonstrates a relationship between specific mutations, severity and clinical outcomes for OTCD patients. For more information, check out the Recommended Reading section.

How many people are impacted by OTCD?

It is estimated that about 1/14,000 to 1/77,000 people are impacted by OTC Deficiency worldwide. This is anywhere from 100,000 to half a million people around the world. It is hard to know the exact number because this condition often goes misdiagnosed and it is not captured in newborn screening testing in Ontario. It is offered as part of newborn screening in some States across the US.

How is OTCD diagnosed?

OTCD is diagnosed via a genetic panel or Whole Exome

Sequencing Test which searches all of our genes (coded areas) for possible mutations. Our genes contain instructions for making different proteins in our body, each with a unique purpose and function. When there is an error in one or more of the genes such as the OTC gene, it can lead to symptoms and disease because a certain protein is impacted - in this case, the OTC enzyme. The result is a change in function or abundance of the protein, and sometimes complete absence of the functional protein.

Genetic variants, or mutations (specific errors in the gene) may impact severity of disease, lead to different symptoms, and varied clinical outcomes. The presentation of symptoms and severity of the disease can vary greatly even within the same family where a few people are impacted by the same type of mutation. Environmental factors and lifestyle choices can further influence the expression or silencing of certain genes.

How is OTC Deficiency managed?

There is no cure for OTCD. The condition is managed with medication or a liver transplant. The medication does not always work and individuals can still get sudden metabolic crises. Liver transplant, while it may correct the urea cycle disorder, is a major surgery and leads to a chronic health condition with life-long immunosuppression. There are various risks associated with this procedure and complications may include organ rejection, cancer, and even death. Furthermore, liver transplant is not the ideal response for OTCD because the OTC gene is expressed in hepatocyte cells in a small part of the liver (peri-portal area). Secondly, and perhaps most shocking, liver donors are not screened for OTC deficiency - the very condition this procedure is meant to treat.

Why did you decide to launch CureOTCD?

CureOTCD was created to help improve and expand treatment options available for children impacted by this severe condition. Currently, the available treatment options are limited. The standard of care for OTCD in Canada and other parts of the world is not good enough. By default, babies diagnosed with early onset OTC Deficiency are prescribed a liver transplant. However, a recent study revealed that there is variation in the clinical outcomes for people with various OTC mutations. For this reason, we believe that each child should be treated with a unique treatment approach, based on their genetic variant, residual enzymatic activity, and specific phenotype.

Research in this area illustrates that some OTC variants may be more severe than others in terms of presentation, disease progression and frequency of recurrent hyperammonemic episodes. This could be due to the fact that various mutations, depending on the type and location on the OTC gene, impact the OTC enzyme differently (for eg. in terms of functionality, structure and abundance). For this reason, we believe that there should be more than one treatment option available to patients to meet their unique needs. Diversifying treatment options will increase the likelihood of finding a cure, or several curative treatments, quicker.

What are other ways I can support your cause if I cannot donate money at this time?

You can share our campaign with friends and family. You may donate items for an auction or future contest draws to help fundraise more money. You can organize a separate fundraiser to drive donations. Some of our supporters took the initiative to run a specialized class in exchange for donations while others offered their service in exchange for funds to support #SaveEtan. We are always looking for volunteers to help with different tasks:

Join us as a Board Member
Help with grant applications and donation request letters to Foundations and other businesses
Engage with our community and build awareness of OTCD
Create promotional and educational material
Help with translation of online content and material to increase our audience engagement

Have an idea of how you can help? Contact us today! We will be happy to hear from you.

How are you spending your funds? What is your research focus?

CureOTCD has partnered with two prominent researchers from the Children National Hospital in Washington, DC: Dr. Ljubica Caldovic and Dr. Hiroki Morizono (link profiles). We are in the initial stages of determining our Strategic Plan and identifying research priorities. The preliminary focus is on using stem cells to test and develop new therapies to treat OTCD in children. The focus of the stem cell therapy - there are two promising approaches we are currently exploring - is to increase expression of OTC enzyme and to restore the urea cycle in the liver.

Another focus for prospective research is drug repurposing. Our scientific group has identified several drugs that are currently available commercially for other conditions (they are proven to work for certain diseases like diabetes) and there is some preliminary data to show they can also be used to protect the brain from hyperammonemia which is a serious risk for OTCD patients.

Equally important, there are other drugs that show promising results through preliminary animal models to increase expression of OTC in the liver. These drugs need to be tested further in the lab using mice models before clinical studies can commence to approve their use for the above purposes. There are costs associated with running animal studies and funding is a barrier. We need to fundraise approximately $100,000 per year for a drug repurposing research project. For updates on research priorities, please visit the Research Focus Page (link).

Do you work with other organizations to advocate for OTCD and support your cause?

Yes, we are members of CanPKU+ Allied Disorders and Global Genes Rare Advocacy Group. We are actively seeking new partnership opportunists and collaborations to increase our impact.