coming out of my shell

coming out of my shell

Sunday, December 28, 2014

The Family Disease

There is a genetic disease in my maternal line called Adrenoleukedystrophy (also referred to as X-ALD).  It is an X-linked disorder that has killed 3 of my male first cousins, at least one of my uncles, and two of my great uncles.   The movie “Lorenzo’s Oil” is about a boy who had ALD.  Lorenzo’s Oil is an important treatment option; however, there is no cure.  Family lore instructed us that females were the carriers and males were the victims of this disease, but it turns out to be more complicated than that.

The disease presents in affected males in one of two ways:
ALD presents in early childhood and is the most severe form.  Affected children usually develop normally until they are about 7 years old.  If untreated before a certain age, the boy will rapidly degenerate to a vegetative state, before which he can go blind and deaf.  My Mom’s youngest brother died from the childhood variant in 1947 at the age of 8.  A cousin of mine died at age 13 in 1991. 

The other variant, AMN (Adrenomyeloneuropathy) usually develops in early adulthood, although it can develop later in life.  It eventually kills the victim, but not before they loose the use of their lower limbs. Another first cousin of mine died at 57 years of age in 2005. Two other male cousins died from AMN in their 20’s. 

My maternal grandparents, William and Veronica, were married in 1910.  Two of Veronica’s brothers seem to have died of ALD, but the disease was not understood back then.  Unbeknownst to her, Grandma was a carrier.  Between 1912 and 1939 my grandparents had 13 children, 5 boys and 8 girls.  The odds are that 50% of these children either had the disease or were carriers. To date, we can identify 3 of their daughters as being carriers because they had male descendants who developed one of the two variants of the disease.  My grandparents also had at least one son who died of ALD (Jerry).  It is likely that two other sons (Edward and Wilfred) had ALD, but they died in early childhood around the time of WWI, and the disease was not understood at that time.  Not every daughter became a carrier, and not every son got the disease.  It was a poorly understood crapshoot.  My grandparents had 36 grandchildren. Since we now know that the children of a carrier mother have a 50/50 chance of getting the disease, and making the very broad assumption that Edward and Wilfred had ALD, it is still possible that one more of their children carried the gene. This is why it is so important that all my living aunts, and my cousins whose mothers and fathers have died, get tested. 

The gene for ALD can act like a terrorist sleeper cell, hiding for years before revealing itself.  For example, my Aunt Rita died in 1958 not realizing she was a carrier.  She had three children, a boy who died at 4 months, and two daughters who are still living.  Both daughters had children.  K had a son and two daughters.  N had two sons.  Since none of Aunt Rita’s 3 grandsons developed ALD, no one ever suspected Aunt Rita was a carrier.  However, in 2013, 55 years after she died (!) and 3 generations out, one of her great grandsons, A, was diagnosed at 8 years old.  Rita had a daughter, K, who had a daughter, KY, who is A’s mother.  It turns out Rita, K, and KY were all carriers, but it hid in their genes until A was born.  

My mother underwent genetic testing in the 1990’s, after a nephew and 2 grandnephews died from this disease.  The results were negative.  Now there is more up-to-date information about the disease, including the fact that the genetic test available in the 1990’s was only 80% accurate. With some effort I was able to convince Mom’s doctor to get her tested again with the new (100% accurate) genetic test.   The trick was to convince the doctor to state it was “medically necessary” to conduct the genetic tests so that insurance would pay for it.  He was reluctant.  He actually said,  “if none of her sons had it then she probably doesn’t carry the gene”…  That is a genetically naive statement, considering my mother had 7 children and 4 of them could be female carriers.   "Probably" does not cut it when you are dealing with the lives of your descendants.  In addition, two of my three brothers died before they were 40 years old.  Remember that one of my cousins did not even develop AMN until he was in his 40s, and some males carry the gene but do not develop symptoms.  Plus, my mother is 88 years old and living in a nursing home suffering the advanced stages of Parkinson’s Disease – one of the diseases that can mimic ALD symptoms.  It seemed to me at least medically necessary to make sure she was not being treated for a disease she did not have.  In fact it is medically necessary to conduct this test simply to determine if any of her descendants are at risk.  I appealed to him on the phone, and sent him tons of information on ALD as well as a long genealogy showing how often it has shown up in our line.  Eventually he came around, contacted the experts at Johns Hopkins and ordered the tests.  I appreciate the fact that he listened and changed his mind when faced with the facts. 

The genetic testing was administered through Johns Hopkins University Hospital in Baltimore. Out-of-pocket it cost a little over $500 because insurance covered most of it.  Once again, her results came back negative.  We are so lucky, and considering the randomness of genetics that is all it can be: cold, impersonal luck.   Good luck or bad luck.  

The information and understanding we had for this disease was limited prior to A’s diagnosis in 2013; however, that limited understanding was simple and easy to ignore.  We used to think that only daughters were carriers and only males got the disease.  So if none of your brothers developed the disease it was easy to make the assumption that your family was safe, until A got it. 

A’s mother, KY, wanted the facts, the figures, and the science in order to help her son.  What she found was disturbing.  Apparently, both men and women can be carriers, not just women.  If a man has the gene then there is 100% chance that he will pass the gene on to his daughters and zero chance he would pass it on to his sons.   If a woman is a carrier then all her children (male and female) have a 50% chance of inheriting the gene.  In addition, some male carriers NEVER show any symptoms but still pass the gene on to their daughters, AND some female carriers show symptoms of AMN as they age.  They can be misdiagnosed with diseases like Parkinson’s or MS.  So unless modern genetic testing is done on the oldest living relative in each of Grandma’s children’s families, we will not know if we carry the gene into future generations or not.  Most of my aunts and uncles in this genealogical line have already passed away.   Unfortunately, that means many of my first cousins still need to be genetically tested, except the sons of sons of Grandma… because although a female carrier can pass it on to both her sons and daughters, a male carrier can only pass it on to his daughters. Are your eyes crossing about now?  Maybe this will help:

  • Sons of female carriers have a 50/50 chance of inheriting the gene
  • The sons of male carriers/victims are always safe.   
  • The daughters of male carriers/victims will definitely inherit the gene and are always carriers
  • Here is the kicker:  Some male carriers do not ever display signs of having the disease, but they still have it and they have 100% chance of passing the gene on to their daughters

  • The sons and daughters of female carriers have a 50% chance of carrying the gene
  • Almost 50% of  female carriers develop some AMN related symptoms as they age
A female carrier would pass the gene on to 50% of her children.   Genetics is a crap shoot.  It could totally skip her sons, but still be inherited by her daughters – giving the illusion in that generation of the family being ALD free.  If the carrier daughter only has daughters, her daughters have a 50% chance and would pass it on to 50% of their children, etc.   This is exactly how A developed ALD 55 years and 3 generations after his great-grandmother died.

I can trace the genealogy of this disease back to a specific male carrier/victim, my great-great grandfather, Tony Mueller.  He would have inherited this disease from his mother.  Tony Mueller was born in 1841 and died of AMN at the age of 39 in 1870.  He was one of 6 children, so he would not have been the only child who passed this gene down.  Odds are that at least 2 more of their children were either carriers or carrier/victims.  Anton had 2 daughters and a son with his wife, Susanna.  Their son was, of course, genetically exempt.  One daughter became a nun. The third child, my Great Grandmother Catherine, married Frank.  Catherine was a carrier. Catherine and Frank had 7 children.  Two of their sons died of what the family believes to have been AMN, one at 39 years old and the other at 19.  Her daughter Veronica (my grandmother) was a carrier.  Another son died at age 15 from a skull fracture.  A second daughter died at age 2 from unknown reasons.  Catherine and Frank’s 2 remaining sons seem not to have inherited the disease.  

It is so hard to wrap one’s mind around all this, but these are the facts.  This is the uncomfortable and complex truth.  I wish it were not true.  I wish it were not so hard to understand or accept.

KY and her mother reached out to every cousin and aunt who still lived, either directly or through other cousins.  She sent a letter outlining the facts.  She urged everyone to make sure the oldest living relative gets tested through the two places in the U.S. who do this specialized genetic test.  She explained that it was more complicated than we previously thought, i.e., almost no one is safe unless the genetic testing has been done on the oldest surviving person in their direct line.

In truth, the mathematical odds are clear.  Out of 13 children, we know for sure that 4 carried the gene for ALD.  It is possible that two more sons had it, but we can never know for sure if they did.  There remains a 50% possibility at least one more child of William and Veronica inherited that gene.  Hopefully the other 50% won out and everyone else is safe, but we cannot live on hope.  The stakes are too high.  

What testing needs to be done?
The following is paraphrased from recent updates written by KY:  

In 2013, the lab tested A's ABCD1 gene to see the exact genetic change/problem that resulted in his diagnosis.  He has a deletion of this gene so testing in other family members must be done by the MLPA - a deletion testing methodology.  There are two labs in the USA that do deletion testing on this gene:  1) John Hopkins DNA Diagnostic Lab in Baltimore, Maryland and 2) Emory Genetics Lab in Atlanta, Georgia.   A's test was done at John's Hopkins; ideally further family testing should be done in the same lab so they will have A's results as a reference.

In November 2013, A underwent a bone marrow transplant at the U. of Minnesota’s Amplatz Children’s Hospital, which is at the forefront of fighting this terrible disease.  It seems to have been successful in stopping further damage.  However, his hearing is completely and permanently gone and he is learning American Sign Language.  Unfortunately, he has also suffered significant vision loss.  The current medications he takes will hopefully stop more damage from occurring, but they cannot correct any damage that occurred prior to the bone marrow transplant.  This is why it is so important to know if our children are potential victims.  Otherwise, by the time the disease presents, it is too late to stop the damage.  In addition, he will remain on hydrocortisone, a steroid, for adrenal insufficiency for the rest of his life.  He is 9 years old.  California and New York State have recently decided to include ALD testing with the routine screening done on all newborns.  Let us hope other states follow suit.

Wednesday, December 17, 2014

Wrapping It All Up

You should see me wrapping Christmas presents this year.  I love Christmas and I really like buying presents.  However, I am SO over the present wrapping thing.  I distinctly remember the great joy I derived from wrapping Christmas presents when I was a teenager.  I always volunteered to wrap the family presents for my Mom, to help her out at a busy time of the year.  I went to great lengths to make each present a work of art.  I made bows with wide ribbon.  I added festive decorations.  They were beautiful.  It was fun.  Unfortunately as I got older, each year I became a little less creative and a little less thrilled with the process.  Now I do not even put bows on the presents.  Seriously.  No bows.  They are just another expense and make for more trash fouling up the environment.  Bah, humbug.  Away with all bows.

I buy the cheapest wrapping paper I can find and I wrap those suckers as fast as I can.  Today I was wrapping like a fiend, trying to get every present I currently have wrapped and ready for the big day.   Because my wrapping paper is so cheap and crappy, when I pull the sides together to seal the package, the paper often rips open at the corners.  HA!  That does not bother the likes of me!  I laugh (ho, ho, ho) as I apply Scotch magic tape and patch up the corners.  I am NOT gonna re-wrap the damn present because of a little, wussy rip.  The grandkids are going to tear open the package wrapping anyway. They will not notice. And if they do, it will be a pleasant Grandma memory they can share with their own kids someday - along the lines of "Your Great Grandma was SO cheap, she wouldn't even ...{insert your own memory}.  I own it.  I enjoy myself.  I am a rebel at heart.

Hey, I think I got this from my own sweet Grandma.  She was a sweet transplanted mountain woman from the hills of Tennessee.  Do not call her a hillbilly, 'cause then I will have to hurt you.  She was, without a doubt, the best person I ever met.  When we moved away from Northern Indiana for a few years in my childhood, she would send us big Christmas packages filled with lots of presents.   None of those presents had bows.  The bows would have just gotten smooshed in the tightly packed box; however, she would not use tags, either.  She would simply write the name of the kid on the wrapping paper.  I wish I would have thought of that, because I also resent buying the stupid tags.  Sometimes you just have to follow your heart and trust your own instincts.  Do not let Hallmark run your life. 

Tuesday, December 9, 2014

Real Life

Have you ever heard a retired person complain about how busy they are and how they do not know how they ever managed work and homelife when they had a full time job?  Yeah, the young me was always rolling my eyes to the back of my head when I heard that.  When you ARE balancing work/family/relationship/home it is too cruel to hear a non-working person complain about being busy.  Imagine my surprise to discover when you stop working "real life" moves in to fill the void.  Still, real life beats the hell out of working for a living.  I am not gonna lie.

I sincerely do not know how I managed to conduct my personal life while working outside the home for 37 years.  In fact, I think maybe I did not have a personal life then.  Something had to go to make time for work.  Working outside the home is all consuming.  The workplace is unforgiving, demanding, and pretty much devours the majority of your daylight hours.  I remember coming home from work and plopping myself on the couch just staring into space, night after night.  "Shaken, not stirred" is how I felt.  It inspired me to start making martinis.  At least that got me up off the couch. 

The last few years of working full-time I was unable to read a book because I was too stressed to focus on a page of text.  Towards the end of my work years I rarely read an email word for word, skimming each one for the punchlines in order to get through them all in a timely fashion.  Weekends were spent cleaning, cooking, shopping, catching up with friends and family.  I guess I was lucky that we did not live near our grandkids then, because when would I have seen them?  Would I have really wanted to add babysitting to that mix?  There was never anytime for myself then.   I ached for retirement so that I could relax and do all those things one is never able to accomplish on a measly weekend.

I went through the working mother routine, too - the years when raising children was supposed to be your top priority.  And I only had one child. When do working mothers sleep? Actually, when they do lay down to sleep they are unable to relax because they are wracked with guilt for not spending enough time with their kids.  But I had my kid when I was 20.  I had an abundance of energy back then.  I felt like I could do it all. What about the mothers who just start having children at 40?  How do they keep from jumping off a cliff? 

Aging is the issue.  I simply do not have the energy I once had.  My mind is going 100 miles per hour, but my body is meandering along at 20 mph. When I was young it was all a game, and I reveled in the challenge.  Now the thought of being challenged makes me want to throw up.  I want time. Lots of time. All to myself.