Symptoms with LRRK2 and GBA mutations

[felixned]

I would appreciate any feedback from anybody who had Fox Foundation genetic screening and happened to have N370S and G2019S mutations. I would like to compare symptoms, medication, etc.

[Lana666]

G2019S - non tremor phenotype, stiffness, bradykinesia, left site mostly affected, dystonia is a big issue. Female, early onset - diagnosed at 52, symptoms several years before diagnosis.

I was tested only for this particular mutation, so can not say anything definite regarding the other.

[felixned in reply to Lana666]

Thank you Lana666. I have similar issues but mostly on my right side. I was diagnosed 3 years ago at the age of 63 but I also had symptoms long before. My biggest issue is balance when Sinemet is off.

[pmmargo]

I have N370S according to "23 and me" (23andme.com).

Diagnosed at 52.

Never swung arm even as young adult.

Only a small amount of tremor on left side (so far)...I'm 58.

Bad balance but I'm able to run. Stiffness. I sometimes notice I'm holding my arms like a prarie dog.

I'm interested in learning more about you and your symptoms.

This mutation is most common among Ashkenazis (which I am) and is also responsible for Gaucher's..a difficult genetic illness (my boss's husband that and PD both)

Best wishes! Paul

[felixned in reply to pmmargo]

Paul,

I was diagnosed with Parkinson in 2015 at the age of 63. It was confirmed by DATSCAN in 2016 which I sometimes use as the zero time of my PD. Looking back I had some symptoms (constipation and loss of smell) for a year or even two prior to the official verdict. I am now 68. I am also an Ashkenazi. I don't have tremor but I have bad balance issues, gait problems, morning dystonia, dyskenisia, frequent insomnia, constipation, loss of smell, excessive sweating , and some other occasional issues like freezing, bradykenisia. I am very sensitive to dairy, animal proteins, and some fats. If I consume these even in small amounts I end up in OFF state unable to move. I am 99% sure that my maternal grandfather suffered from PD although he never had official diagnosis. He lived to be 92 btw and had tremor. He also was a heavy smoker. I had 1 or 2 months of acute neurological illness prior to slipping into the chronic disease. I take 2-3 100mg sinemets and 8 195mg Rytary daily. I also take some supplements (2 g B1, d3 and others). My disease is progressing quite rapidly judging by the change in my medication and by changes in the symptoms.

Felix

[lenamm]

I have both mutations, my symptoms started at 41 suddenly. I am mostly tremor, dystonia and dyskinesia. I can only take Sinemet ER at very low dose. No balance issues at all.

[Justme4]

My testing from 23 and me came back that I dont have the gene they tested for Parkinson's or cancer.....I d had cancer and I have parkinsons

[Missy0202]

I was tested through my movement disorder specialist when I was diagnosed a year ago. It took a year to come back positive for LRRK2. I don't see N370S and G2019S mentioned on the report.... are those mutations part of LRRK2? I was also tested through the Fox Foundation but didn't get that result back yet. I am Ashkenazi as well

[felixned in reply to Missy0202]

Hi missy0202, I too had genetic test repeated through my neurologist. It confirmed the fox or to be .more precise 23andme results. BTW that's where you find the readable results that are easy to understand.

[Missy0202 in reply to felixned]

The results I got from the Lifelabs genetic only states "autosomal dominant PARK-LRRK2" is confirmed. Would the fox results go into more detail about N370S and G2019S mutations? Thanks Felix

[felixned in reply to Missy0202]

Yes, 23andme has a detailed explanation of the genetic mutations you have that correlate to higher incidents of Parkinson. If you have done genetic test through Fox you should already have 23andme account. How long ago did you do the test? Typically it takes about 1 month for them to display your results. Log in to your account, click on Health & Traits tab and select All Reports. The third line should read Parkinson Disease and whether you are at increased risk. You can then look at the explanation of the mutations as they relate to PD. Also they used to offer free genetic consultation with the genetic specialist from Indiana State Univ if I am not mistaken. May I ask you what symptoms you experience and whether medication is helping

[Missy0202 in reply to felixned]

You’ve been very helpful! Thank you! I lack the arm swing and tremor on my right arm. I started sinemet 25/100 about 7 months ago and it does control the tremor quite well. I am In the midst of a cbd/thc trial and I have to say that I see a huge improvement in the pain and rigidity as well. Sleep is perfect since on the oil as well.

[Missy0202]

Hi and hope you are safe and doing well. I finally got my results from the Indiana University genetic testing and indeed I have the G2019S mutations of LRRK2. No GABA. The genetic counsellor was really helpful and so empathetic

[felixned in reply to Missy0202]

Missy0202, it's useful information (for you). It could make you eligible for some clinical trials and also somewhat useful to predict phenotype of your disease. If you have children it gives them an option to make more informed decisions.

[pmmargo]

please read this: ncbi.nlm.nih.gov/pmc/articl...

we are super fortunate it seems.

Paul

[Missy0202 in reply to pmmargo]

Hi Paul. Can you brief me on why we are fortunate to have LRRK2? I attempted to read this but my mind can't comprehend 😔

[pmmargo in reply to Missy0202]

Sorry ..it is the N370S mutation you might be fortunate to have. According to the paper it is a fovorable mutation. It might mean that ambroxyl would work on the person with it and also such person would not get dementia as early as otherwise. Best wishes! Paul

[Missy0202 in reply to pmmargo]

Ok got it. Too bad for LRRK2 😞

[pmmargo in reply to Missy0202]

Sorry I did not read more carefully. It is felix and I that should be celebrating. I missed the words "No GBA". Best wishes! All the ones of us with mutations will be the first to benefit since they already have gene therapies for a lot of the mutations. SO as long as we don't get cytokine reactions we could be cured in principle.

[Missy0202 in reply to pmmargo]

Thanks for the clarification and for giving me some hope

[pmmargo]

Dear Felix, It looks like the Russian scientists are recommending ambroxyl for us.

It is cough syrup from the phillipines. I'm consulting with Torres-Yaghi first out of caution but it is over the counter in most of the world. Best, Paul.

[pmmargo]

tons of data on your snp here: snpedia.com/index.php/Rs346...