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OTC Questions from Jane Wright Earl Descendants


1. How do we know this is specific to our family gene mutation?

The family gene mutation is located on the OTC gene. Mutations on this gene affect/reduce the activity of the OTC enzyme which causes the disease.

2. What are the specifics of the mutation?

The mutation is called c.-106C>A. It is located in the promoter region of the gene, meaning it is like a light switch that helps to activate the gene. So at position -106, where there should have been a cytosine, there is an adenine. This shift is like a spelling mistake which causes the DNA to not provide the correct instructions to make the enzyme work as it should.

3. What makes our mutation unique?

It is associated with a late onset variant of the condition which is less common then the classic form of OTC deficiency.

4. How did this mutation start?

We all have changes in our genes that occur as we are developing. The very first person affected in the family had this change occur spontaneously. There was nothing that could have prevented it or anything that the individual could have done differently. Once that individual was affected, it was then passed in the family.

5. Can I use the results from my 23 and me genetic kit to determine if I am negative or positive?

No, this requires a more specific look at the family mutation than the 23 and me kit does.

6. What age does OTC start?

If an individual has OTC, they are born with it. When symptoms start is variable.

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7. If I am positive, what is daily life like?

I wouldn’t expect that your daily life would change. We do recommend avoiding steroids. Treatment differs on gender and the situation. See fact sheet.

8. What are triggers?

Significant illness, long periods of fasting, possible very high protein intake, oral and IV steroids.

9. How long after a trigger will the symptoms appear?

Typically pretty soon in the process. Though if ammonia levels are elevated, often times loved ones around then notice before the individual.

10. Are women affected in anyway?

See fact sheet

11. How do men differ from women in regards to this defect?

See fact sheet

12. Is there any way I can have access to an ER protocol if symptoms appear?

Yes, this can be provided by the local genetics clinic and is typically given at the first clinic appointment and placed in the electronic medical record.

13. After successful treatment of my ammonia levels, what will my recovery entail or be like in the days, weeks or months following?

This depends on how high and for how long ammonia levels are elevated. A short and small increase of ammonia will have a very short recovery time. A very high ammonia, especially one that was high for a long period of time, can take much longer to recover from.

14. How important are hydration, diet and exercise for the prevention of OTC?

Avoiding dehydration and long periods of fasting are recommended. Unless one is doing extreme exercise there should not be concern about exercise. In general, a well-balanced diet is recommended unless you have been instructed otherwise by your genetics clinic or metabolic dietitian.

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15. Can an episode be prevented?

Yes. Avoid oral and IV steroids. During illness, avoid fasting. Focus on getting enough liquid and calories to prevent your body from breaking down its own protein (muscle) which causes an increase in ammonia. If you’re unable to keep down foods and liquids, then seek help at an emergency room with your protocol to receive IV fluids with sugar to provide calories.

16. Would an ID of some kind be useful?

A medical alert bracelet would be helpful to notify emergency personnel.

17. What medication is available?

If needed, medications in this condition are ammonia scavengers (buphenyl and ravicti), citrulline to continue the urea cycle, and possibly other supplements depending on diet and labs.

18. How do they work?

Ammonia scavengers grab on to excess ammonia to reduce levels, citrulline helps to continue the urea cycle on past the metabolic block and also helps a little to reduce ammonia.

19. What determines if I need medications?

Typically labs

20. Who will prescribe the medications?

Your local genetics clinic.

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21. How frequently do I need to be retested?

If you have the mutation and are seen in clinic, it depends on initial labs and treatments needed. If you don’t have the mutation, you do not need to be retested.

22. How does pregnancy affect OTC?

Typically pregnancy goes okay, however delivery can be difficult because of the stress placed on the body. With late onset OTC, there may be no issues, though monitoring in the postpartum period of any concerns could be warranted.

23. When should a newborn be tested?

As soon as possible, especially for males.

24. When they test my blood how do they detect if I am negative or positive to our family gene mutation?

The blood test looks at the specific gene that causes the condition to see if it has a mutation which would cause the disease.

25. Is autism affected by OTC?

If a child has had frequently elevated ammonia levels, developmental delays can be seen.

26. If I am positive, is my treatment going to be the same as the treatment plan for other members of my family who are also positive?

Not necessarily, especially depending on gender.

27. Why should I be tested if I have never had symptoms, am a male with no children?

With the late onset variant, it is possible to be affected and not had symptoms. Especially if you have never received steroids or had a significant illness.

28. If my cousin or siblings have been tested, can I just follow their life style and treatment plan?

No, testing and a visit with the metabolic clinic is necessary to determine your specific treatment plan.

29. Will avoiding protein prevent an episode?

No, in fact- not enough protein is not good for the body with OTC either.

30. If my blood was tested 30 years ago and I am negative, do I need to be tested again?

Probably, this gene change was just found this year after several years and studies over the last couple of decades.

31. If I was tested through a urine test, do I need to be tested through a blood draw?

Yes, there is no urine test for DNA studies.

32. What research has occurred and what future research is being carried out today?

Research has focused mostly on drug therapies for the condition. However, research regarding RNA and gene therapies are being done on other conditions and could be utilized in the future for OTC deficiency.

33. Is the internet a good resource?

In general it depends where you are looking. Peer reviewed journal articles are always the best resource.


 
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