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Understanding Urea Cycle Disorders
A urea cycle disorder, or UCD, is a genetic disorder that a child is born with. When food that has protein in it enters the body, its 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 cant 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 cant get rid of it.
Image from Horizon Therapeutics
Metabolic stressors viruses, high protein intake, excessive exercise or dieting, surgery or certain drug (valproic acid, prednisone or other corticosteroid) can create excessive ammonia, resulting in severe neurological symptoms.
Types of UCDS
- 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 doesnt 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.
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 treatments and therapies in Canada.
Learn tips and tricks for eating a low-protein diet.
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
How UCDs relate to other metabolic disorders
Image credit: flok
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
Resources and support
Websites you may be interested in
National Urea Cycle Disorders FoundationA non-profit organization dedicated to saving
and improving the lives of children and adults from the catastrophic effects of
UCDs. | Connecting Families UCD FoundationConnects families and provides support and
critical tools to enhance quality of life for those with UCDs. | Urea Cycle Disorders ConsortiumA team of physician scientists,
neuropsychologists, nurses, genetic counselors, research staff and patient
advocates throughout the US, working together to improve the lives of people
with UCDs. They collaborate with sites in Canada. |
Remember The Girls Committed to advocating for females impacted by
X-linked conditions. | UCD in Common Information on UCDs, including genetics,
management and caring for children, by Horizon Therapeutics. | flokCreated for families with UCD, PKU |
Metabolic Support UKCheck out the Think Ammonia campaign resources specifically for Canada. |
Opportunities
Learn more about how you can help the UCD community:
Research
- Urea Cycle Disorders over time: What were 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?
- VIDEO: Understanding and participating in clinical trials
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. Dudleys 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 dont work reliably for all UCDs, including OTC). They are also looking to use the technique to better understand and diagnose other UCDs. Learn more
Liver transplant
- Making the Choice - Medical
Management or Liver Transplant for UCDs: The Family Experience
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
- VIDEO: A long-term perspective on liver transplant decision making in UCDs
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
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
- 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