Sunday, May 9, 2010

The Natural History of Kennedy's Disease

Dr. Lenore Beitel was on our chat this last Saturday.  A question was asked about whether there was any correlation between the CAG – repeat length (the number of CAGs) and age of onset and progression.  Dr. Beitel responded that there was a study in Japan that was published four years ago that answered this question.  Dr. Beitel was kind enough to send me the link to the transcript and I downloaded it.  When I saved the PDF, I was told I already had that file (Yup, I totally forgot).  Well, I read the article again Sunday and found it worthwhile and in need of sharing with others.
The study is titled, “Natural history of spinal and bulbar muscular atrophy (SBMA): a study of 223 Japanese patients.”  Several doctors including Gen Subue performed the study.  There is no cost to read or download the report.
Fortunately, this study is well written … meaning I could understand it.  This is the only study that I am aware of that focuses in on what happens and when does it occur.  It is based upon data provided for up to twenty years of a patient’s life.  This study is different than most, because of the number of patients.  So often the patient base is substantially smaller.  I would recommend reading the article if you want to learn more about the onset and progression of Kennedy’s Disease.  Little time is given to the cause of Kennedy’s Disease or current research if that is your interest.  Below, I will summarize what I found interesting.
Of the 233 patients, the average age was 55 with a range from 30 to 87.  The average CAG-repeat length (count) was 46.6 with a range from 40 to 57.  The initial muscular weakness perceived was in the lower extremities (70% of the time) even though some patients noticed weakness in two locations at the same time.
In my opinion, the key findings in this study were:

1.  The greater the size of the CAG-repeat expansion (CAG count), the earlier the onset.  The study used nine ADL’s (activities of daily living*) for milestones in this study.  The age of onset of these nine ADL milestones were evaluated in the 233 patients.  ADL’s include:
a.       hand tremors
b.      muscular weakness
c.       requiring a handrail to climb stairs
d.      dysarthia (speech issues)
e.      dysphagia (swallowing issues)
f.        use of a cane
g.       use of a wheelchair
h.      pneumonia
i.         death
2.  The rate of disease progression was not dependent upon the number of CAG-repeats.  This was very interesting to me.  One you began to see symptoms, the progression appears to be fairly well defined.  (See the next bullet)
3.  The researchers commented that the most striking observation was that the CAG-repeat length did not affect the interval periods between the individual ADL milestones.  In other words, the progression of the disease is not influenced by the CAG count.  Once a patient reached one milestone, the length of time to the next milestone was similar to the other patients regardless of the count.  The thought here was that progression from degeneration to cell death might be determined by intrinsic factors such as a “cell death processing system” (I am not certain what this means).
4.  The most common cause of death was pneumonia due to aspiration and dysphagia.  Even though these two bulbar symptoms were relatively mild when first manifested, they were serious issues in the later phases of the disease.  I always knew that pneumonia was bad from a personal family experience and from comments of others living with the disease.  This point reemphasizes the need for flu and pneumonia shots as well as constant vigilance in regards to any signs of these health concerns.
5.  Creatine kinase (CK) averaged 863 in these patients with a range from 31 to 4955.  A reader asked a CK question recently and all I could comment at that time was based upon personal history.  The normal range for CK is 45 to 245.
 6.  Serum testosterone levels were relatively high even with older patients, although the levels did decrease with age.
Of the key findings, I expected #1, but was surprised about #2 and 3.  These two were probably the most interesting to me.  #4 and 5 were not a surprise, but #6 was unexpected also.  Because of the size of the study group and the consistency in certain results, I believe the information will help many of us living with Kennedy’s Disease to understand the phases of the disease.  In a few weeks, I will read the report again to see what else I can glean from it.
* Note:  Certain other symptoms were left out of this study because patients were not always aware of them (or when they started) even though they might be present.  They include muscle cramps, muscle exhaustion, difficulty chewing, fasciculation (muscle twitch), and gyneconmastia (enlarged breasts).

I would be interested in your thoughts after you read the study.  Did you find the report interesting?  Did anything surprise you?  Will the findings change anything in your life? 


  1. Hi there - I like your blog & now I have subscribed through Google read it regularly.

    Yes this was a well written & easy to read article. I'e only speed read it but the points of interest to me were:
    1. How totally typical are my symptoms
    2. How much younger than me most people were when they were first identified. My brother & I both first became aware of it in mid to late 50ies
    3. How relentless the progress is - I'd kind of hoped my progression would be slower than average :-)
    4. How critical it is to avoid pneumonia (I've had it 3 times - the first was very serious but that time years ago I was marathon running & thus able to get over it).

    Good luck & keep it up

    Bertie B

  2. Thank you, Bertie

    I appreciate your kind comments as well as your perspective on the disease. I believe reading the study makes you consider your onset and progression. In my Tuesday post I will do more comparisons to my situation.

    If you come up with other thoughts, please let me know.

  3. Thank you it was a very good reading. My husband has kennedys and is 48 he found out he had kennedys about 4 years ago.
    Thank you

  4. Bruce - this was a really interesting article. I was dismayed when I first read it as it seemed to indicate quite a standard and relatively fast transition between the stages.

    I am 61 and was offically tested positive for KD about 6 years ago. First symptoms e.g. cramps were probably in my late 30s. Thankfully I do not appear to have deteriorated in the last 10 years. I test myself climbing up/down the stairs 5 times not using a hand rail every few months to be a little more objective.

    I realise I am very fortunate and know things can change quicky. I exercise at the gym 3 times a week and in particular, use a vibration plate machine with my exercises. It could be coincidence but I have a feeling exercise is very important to KDers especially in the early stages. This may not appeal to others but I pray and feel God has a role for me in the voluntary work I do. This seems to take my mind off the future path of KD.
    I think these reports are useful but we should bear in mind that there seems a wide probably unexplainable variation in each of us as individuals.

  5. JoAnn, thanks for reading my blog and commenting. I recommend that you and your husband read my "Document Everything" - Part I and II articles. It could be important and needed someplace down the line.

  6. John, you are doing great! Thanks for reading and commenting on my article.

    As you probably know, I am an advocate of exercising. I commented several times that "smart" exercising is an excellent way to keep the motor neurons firing and muscles stimulated.

    Yes, you are right about a wide range. I mentioned in an article several months ago that there is nothing uniform about symptoms, onset, and progression for people living with KD.


Please feel free to comment. By taking a moment to share your thoughts you add much to these articles. The articles then become more than just something I said or believe. In addition, by adding a comment, you might just be helping the next reader by sharing your opinion, experience, or a helpful tip. You can comment below or by sending me an email. I look forward to hearing from you.