Urea Cycle Disorders (UCDs)
Hello, my name is Michaela Garstin and I'm the Chair for UCDs.
We found out our daughter has Citrullinemia (a type of UCD) through newborn screening when she was a week old. She's six years old now and has been on a low-protein diet her whole life.
I like to say that she's my little chef because she loves cooking and trying all kinds of new low-protein food. You can often find us trying a new recipe at home or dining at a restaurant, carefully watching her protein intake of course!
I'm looking forward to helping fellow Canadians in the UCD community. Please feel free to reach out to me at ucds@canpku.org.
Join our UCD Facebook group to connect with other Canadian families!
What is a UCD?
A urea cycle disorder, or UCD, is a genetic disorder that a child is born with. The child inherits a defective gene(s) from their parents. People can be diagnosed with a UCD at any point in their life.
When food that has protein in it enters the body, it’s broken down in the digestive tract. In a person with a healthy urea cycle in their liver, toxic ammonia is turned into urea so the body can get rid of it naturally.
When a person has a UCD, the urea cycle can’t change the ammonia into urea as well as it should. Ammonia builds up in the blood, and can travel to the brain, because the body can’t get rid of it.
Image credit: Horizon Therapeutics
Metabolic stressors – viruses, high protein intake, excessive exercise or dieting, surgery or a drug (valproic acid, prednisone or other corticosteroid) – can create excessive ammonia, resulting in severe neurological symptoms.
Types of UCDs
The name of the UCD is based on which enzyme or transporter isn’t working properly in the urea cycle:
- OTC – Ornithine transcarbamylase deficiency
- CPS1 – Carbamoyl phosphate synthetase 1 deficiency
- Citrullinemia Type 1 – Argininosuccinate synthetase deficiency
- ASA – Argininosuccinate lyase deficiency
- ARG – Arginase-1 deficiency
- NAGS – N-acetylglutamate synthase deficiency
- HHH – Hyperornithinemia-hyperammonemia-homocitrullinuria syndrome
- AACD – Adolescent and adult citrin deficiency (formerly Citrullinemia Type 2, Citrulline deficiency)
UCDs are genetic
UCDs happen when one or both parents pass down a defective gene that doesn’t work properly in their child. Rarely, a UCD is caused by a random mutation.
OTC is the most common type of UCD. It is x-linked, which means the gene is typically passed down from a mother to her child. Unfortunately, this condition is not included in newborn screening testing in Canada.
The other UCDs are autosomal recessive, which means that two parents, who are both carriers, pass down the gene to their child.
Symptoms
UCDs affect everyone differently, including the severity. Some people have never had high ammonia thanks to being diagnosed through newborn screening, while others have had multiple high ammonia episodes and require medication – and everything in between.
Common symptoms of high ammonia levels include:
- Vomiting
- Headaches
- Aggression
- Feeling very tired
These symptoms can be a sign of a hyperammonemic crisis (extremely high levels on ammonia), which is very serious and needs immediate medical attention because it could cause coma, brain damage of even death.
Other symptoms of UCDs include:
- Moodiness
- Forgetfulness
- Short attention span
- Trouble with problem solving
- Lack of appetite
Most people present with symptoms outside the newborn period (28 days+ after birth). We are seeing more asymptomatic patients thanks to newborn screening being available for some UCDs.
*Data from a longitudinal study of 614 patients conducted by the UCDs consortium, a member of the NIH Rare Disease Clinical Research Network.
Image credit: Rare Diseases Canada
Treatment
There are options to help control high ammonia levels, including:
- Low-protein diet, which can include lots of vegetables, medical food and formula
- Amino acid supplements
- Ammonia-controlling medication
- Liver transplant
Learn more about working being done to cure early-onset OTC at cureotcd.com.
Newborn screening
Only Citrullinemia Type 1 and ASA are included in newborn screening in Canada.
Unfortunately, newborn screening is not available for OTC, the most common type of UCD. Learn more: Point-of-care screening and clinical considerations for OTC deficiency: Is Newborn Screening Ready?
How UCDs relate to other metabolic disorders
Image credit: flok
Resources
General information
UCD guide for new families in the USA - National Urea Cycle Disorders Foundation
UCD guide for new families in the UK and Europe - National Urea Cycle Disorders Foundation
Fact Sheet on UCD - Nutricia
Low Pro Local Food Catalogue - IWK Health
School support
A Teacher's Guide to UCDs - National Urea Cycle Disorders Foundation
Educators Guide to UCDs (Perfect for school nurses and IEP facilitators) - National Urea Cycle Disorders
Ammonia testing
Make sure your ammonia level test is done properly. Print these instructions and bring it with you to the lab or email ucds@canpku.org with your mailing address address and we will mail a couple handy wallet-sized brochures to you!
Nutrition
UCD Food Guide - Abbott
Low-protein recipes and shopping list - UCD in Common
Medical food - most provinces provide a yearly allowance for low-protein medical food (i.e. pasta, cereal, etc.). Check with your clinic for more information.
Videos
Behind the Mystery: Urea Cycle Disorders
What is a Urea Cycle Disorder? - Horizon Therapeutics
Mitchell's story of a rare genetic disorder and clinical trials participation - National Urea Cycle Disorders Foundation
Zoe's story: Swift identification of elevated ammonia levels is needed to save lives - National Urea Cycle Disorders Foundation
Disability tax credit
The Disability Tax Credit is available to Canadians of all ages with a metabolic disorder involving consuming low-protein foods that require measuring, special preparation and ordered through a medical clinic.
No one who has followed our advice has been refused! Our success rate is 100%, meaning we have directly helped 150+ families and adults living with PKU or an allied disorder get approved. Learn more.
Other websites
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National Urea Cycle Disorder Foundation (USA) Urea Cycle Disorders Consortium (USA) |
Connecting Families UCD Foundation (USA) UCD in Common (USA) flok (USA) |
Remember The Girls (USA) cureotcd.com
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Research
Learn more about the important research being conducted on the US-based National Urea Cycle Disorders Foundation website.
Urea Cycle Disorders over time: What we’re learning from a natural history study
Suggested guidelines for the diagnosis and management of urea cycle disorders
The management and clinical outcomes of pregnancies in women with urea cycle disorders
VIDEO: Emerging knowledge from MRI studies: Is ammonia control enough? - National Urea Cycle Disorders Foundation
VIDEO: Understanding and participating in clinical trials - National Urea Cycle Disorders Foundation
Research aims to improve diagnosis of OTC and other UCDs
Fast and accurate diagnosis of OTC may finally be within reach, thanks to the power of yeast genetics. Many of the same metabolic processes that happen in a human cell, also happen in a yeast cell.
Dr. Dudley’s team measured the activity of 1,570 OTC variants, ranked them by severity and evaluated how well the results agreed with the experiences of patients.
A panel of experts is already considering the data for clinical use in diagnosing OTC (the dried blood spots used in newborn screening don’t work reliably for all UCDs, including OTC). They are also looking to use the technique to better understand and diagnose other UCDs.
Liver transplant
Making the Choice - Medical Management or Liver Transplant for UCDs: The Family Experience - National Urea Cycle Disorder Foundation
If you would like a hardcopy, please email ucds@canpku.org with your mailing address address and we will mail one to you.
VIDEO: Making the choice between medical management and liver transplant - National Urea Cycle Disorders Foundation
VIDEO: A long-term perspective on liver transplant decision making in UCDs - National Urea Cycle Disorders Foundation
Liver disease
Dr. Lindsay Burrage's research explores whether tools that don't require taking a piece of liver tissue can be used to measure liver fibrosis in UCDs. She shared that everyone with a UCD is likely to have some risk for liver disease and suggested they talk to their metabolic doctor for tips on keeping their liver as healthy as possible.
VIDEO: New insights on liver disease in UCDs
Driving
During a focus group of adult with UCDs, researchers found out that at least 50% of them decided to never drive or stop driving. UCDs are associated with executive dysfunction, which can affect driving, and the researchers investigated the use of fNIRS (a brain monitoring technique seen in the photo below) to simulate driving experiences.
Patients with urea cycle disorder struggle with driving: A review
Current clinical trials open to Canadians
Ultragenyx clinical trial - gene therapy for OTC
Please note, this clinical trial is for people with late-onset (after 30 days) OTC diagnosis who are 12 years of age of older. Please contact TrialRecruitment@ultragenyx.com for more information.
Arcturus clinical trial - mRNA therapy for OTC
For more information about the trial below, please email Community@ArcturusRx.com.
Bloomsbury Genetic Therapies clinical trail - gene therapy for OTC
Please note, this clinical trial is for ages 6 to 16. The second phase will be for newborns to 16 years old. The trial is based in London, UK, however it is open to Canadians and travel costs will potentially be covered.
For more information, visit the Metabolic Support UK website or email contact@metabolicsupportuk.org.
In the news
Canadian news
Liver transplant saves young Moose Jaw boy's life
Promising gene therapy for B.C. man with rare genetic disease
1st Canadian patient to receive new liver therapy doing well
Five-year-old girl with rare disease enjoying 'small miracles' after transplant
International news
Desperately ill baby healed with personalized gene therapy, doctors say
Yeast genetics collaboration yields hope for improved diagnosis of urea cycle disorders
Protein drinks should carry warning after boy died, says coroner
Why a bodybuilder's death has been blamed on excessive protein shakes
Father of high school quarterback Robbie Roper speaks out about the real cause of player's death
Australian bodybuilder with rare disorder dies from high-protein diet
Japan newborn gets liver stem cells in world first
Jackson Fukuda wins rare artist award
Complete stranger donates 'sliver of liver' to girl with rare life-threatening liver disorder
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