Meet Three Siblings Fighting Cystinuria

Originally posted on Global Genes in 2012
Note: There is an update to this story HERE

If you have ever had or known someone that had kidney stones, you may understand the excruciating pain associated with these monsters.  The pain has been described as the worst, unbearable pain that you could ever feel.  Some say “it has brought grown men to their knees, begging for relief in the local Emergency Room.” Others say, “they have actually passed out from the horrible pain they bring.” Imagine living your life with a disease process that produces kidney stones constantly. Unfortunately, there is such a disease process called Cystinuria and again, unfortunately, I have three children that suffer from this awful, debilitating  disease.

It seems like yesterday when I was lying beside my then six year old daughter as she rolled around in her hospital bed with pain from acute pyelonephritis.  I was trying to focus on my little girl while digesting some information the doctors gave me, “all three of your children have Cystinuria.” I was in shock.  How could this be?  I am a nurse.  I know about this rare disease.   I even felt a sense of guilt for this disease is hereditary and my mother suffers from it.  Visions of nursing school flashed through my mind.  I remembered the research I did, the papers I wrote, and the doctors I questioned to help my mother.  Unfortunately, 20 years ago they knew even less about Cystinuria.

In the years before my children were born,  I was adamant about my 13 nieces and nephews being tested.  I guess because none of them were positive and  it was such a rare disease I though I would never pass this on to my children.  I was even told that if my husband were too a carrier we would only have a chance of one out of four of my pregnancies for this to occur.  Well, we beat the odds, but oh how I wish it were in the lottery or something on a more positive note.

After digesting all the news, I could see it all made sense.  The symptoms were all there over the years. A month earlier my two year old son presented with gross hematuria (blood in the urine visible to the eye) with no explanation.  My four year old daughter also had urinary symptoms (burning and frequency) since age two that the doctors referred to as  psychological since there was no infection detected.  She was even hospitalized at three weeks of age for a high fever (105F) of unknown origin. To this day her fever was not understood.

Then my six year old daughter’s symptoms help complete my confirmation.  Not only was she trying to pass several kidney stones but her backaches were there for a reason.  It is called Renal Colic.  Renal Colic is a chronic spasmotic, sharp, stabbing  pain or ache in the back or flank over the kidney region that is present in Cystinuria or other kidney diseases.  This is rare in children so now I knew the reason for her pain.

Cystinuria is an autosomal recessive, metabolic disease that inherently affects the kidneys.  Autosomal recessive means that a person with the disease has inherited two copies of a defective gene.  It affects only 1 out of 15,000 people worldwide and if you do the math this is 150 people out of a million.  Wow, here I am with three children and a mother (who is recovering from a renal transplant from the excessive stone damage all her life) who all suffer from this dreaded disease. It just doesn’t seem possible.

Cystine is one of the essential amino acids which are the building blocks of protein. The defect is simply that they cannot metabolize this amino acid properly (along with three other amino acids: lysine, arginine, and ornithine).  The genetic defect impairs intestinal absorption and renal reabsorption of cystine.  Cystine is then excreted at high levels through the kidneys and is insoluable (meaning not able to dissolve).  In this environment the cystine cystalizes forming stones and potentially causes damage to the kidneys.  These stones can be small or large and can form anywhere in the genitourinary tract (bladder, ureter, and kidneys).

The larger stones may at times require surgical interventions although surgery is made to be the last resort because of their repetitive nature.  Cystine stones form quickly, sometimes just overnight, unlike other calcium oxalate stones which can take years to form.  The bottom line is that a cystinuric person can expect a lifetime of producing kidney stones.  My mother used to joke with us saying she could have probably graveled her driveway with the many stones she has passed over the years and my 14 year old is on her way to doing the same passing over 1000 stones in a seven year period.

Unfortunately, there is no cure for this disease.  There are only two medications (Thiola and d-Penicillimine)  that may help with the concentration of cystine but their side effects are horrifying.  My eldest daughter has been taken off of both due to some neurological side effects (peripheral neuropathies of her lower extremities) and my son was taken off the d-Penn for a lupus erythematous reaction.  The awful thing is that off the medication she produces urine with the consistency of sand constantly.  These medication decisions haunt us periodically because we have to decide which is the lesser of two evils-the painful, damaging stone production or the possibility of more medication side effects.

Another avenue of treatment and most importantly is prevention.  One way we can do this by keeping the GU tract in an unpleasant environment for the stones to form. Cystine stones would normally love an acidic environment, which a normal urine pH is.  So we raise the kids’ pH with medication, Urocitrate-K, to make the urine more alkalitic while raising their citrate level which helps as well.

The most important factor of prevention is that of water consumption.  My children can NEVER be in a dehydrated state.  Just a simple cold or flu virus sometimes scares me to death.  Optimally, my children must consume 4-6 liters of water (fluids) a day, everyday to make the cystine less concentrated or their urine more dilute.  Let’s just say water is our friend.  You will never see my kids without a water bottle in hand.  I always joke about doing a commercial spot for one of the bottled water companies someday.  One positive outcome I noticed of this was a contagious trend.  Over the years I noticed some of their friends carrying water bottles too.  This makes it more normal for them to see their friends doing the same thing.

This turns to another issue my kids face which is normalcy.  Cystinuria is a lifetime disease process so normalcy is a concern for me to foster in my children, especially in the teenage, peer pressure, rebellious ages that lie ahead.  I have already seen some psychological effects with my eldest who has missed on average 30-40 days of school a year not to mention the other functions she misses because of pain, doctor’s visits, tests, hospitalizations, and surgeries.  Fortunately, all of my children have been blessed with the gift of intelligence and music which does help them cope a great deal with all that comes their way.

Whatever stage of development my children my be in, I have learned that there is a great deal to living with any child with chronic health conditions.  Acceptance is a hard one for me.  I tend to have mixed feelings most of the time.  I feel sad and devastated but happy that my children are here with me able to walk, talk, and smile. Sometimes anger plays a part of my dealing with it. Never once do I want to hear the words, “just be grateful it isn’t something worse or life-threatening.”  I have heard this many times, even by family members.  I think to myself , what a terrible thing to say to me.  Here I am with three children that now have imperfections and medical issues not knowing what lies ahead.  How could anyone compare us to those others not so fortunate.

Luckily, these angry feelings do not come by often anymore.  However, I do at times find myself looking at healthy children with no medical issues and wish it all back.  But when I tend to feel this way I always rely on my faith in God and know He is always by our sides through everything that happens in our lives, good or bad.  I also remind myself everyday that this is not about ME.  This is my children’s lifelong struggle.  I am just blessed that I can be here for them in body and spirit and have medical knowledge as a Registered Nurse to teach and guide them in the best way possible.

The hardest thing for me is to live every day wondering if this may be the day that one of them develops pain indicating another kidney stone.  It’s almost like there is a constant time bomb set in my house and we wonder when it will go off.  I wonder to myself, “which one did not drink enough water today?’, “did I forget to give one of them their medication?”, “is their pH alkalitic enough?”, or “am I doing all I can to prevent them from forming stones?”.  I hate the words, “Mom, my pee burns” or “Mom, my back aches” and mostly I hate to see one of them standing over my bed crying hysterically in the middle of the night holding their back knowing this usually leads us to Pittsburgh for treatment, hospitalizations, and possibly surgical interventions.

But most of all, I hated to hear the words of my then ten year old daughter asking me, “Mommy, why does God hate me?” as she dealt with her excruciating pain in the hospital.  This had to be one of the worst things any mother would want to hear.  It really put me on the spot to think and come up with an answer for her. Unfortunately, at that moment it left me speechless.

It wasn’t until 3 o’clock in the morning when I was woke up by my racing thoughts, that I could sit down and write her a book called, “Mommy, Why Me?”, to try and answer her most difficult question.  I prayed a lot and hoped to answer her question correctly knowing that this question would probably enter her mind again and again as well as my other two children’s minds in the future.

Speaking of the future, there are moments I try to envision our future.  What will it be like for my children?  The fear of the unknown haunts me knowing that this disease peeks in the second and third decade of life as it did for my mother.  This may mean more stone formation, more hurting, even possibly more hospitalizations or surgical procedures.  My mother’s unfortunate fate, because of the lack of knowledge and poor medical management, led her to a kidney transplant to treat her acute renal failure.  Miraculously, my wonderful sister was able and willing to donate her kidney.  What an altruistic act on her part and is another story in itself.

It just takes me to all the potential heart-aching possibilities of the future for us.  Not wanting to see all the case scenarios, I quickly come back to present day and press on to just deal with today. However, I am dealing with my children’s Cystinuria, I know I will always be focusing on the knowledge and research aspect of it.  Initially when I found out, I felt helpless, like no one was experiencing what we were going through.  Not even my family.  I contacted the government, The National Organization for Rare Disorders (NORD) and The Research Trust for Metabolic Diseases in Children (RTMDC) for help.  I even found a research physician in Germany who supplied me with a wealth of knowledge related to ongoing research and future endeavors.

Then I found a group called Cystinuria Support Network (CSN) online which has become my savior at times over the past seven years.  CSN was founded and established in 1994 by Jan Ledbeter, a mother of two cystinuric daughters, like myself, who was desperately looking for answers, research, support, and hope for this genetic disease.  Although there are only approximately 400 members worldwide in the group, they provide me with an abundance of knowledge, resources and experience dealing with Cystinuria.  I have learned that no one can truly understand the issues of this disease like those sharing in the same experiences.  This too can be an important life lesson for all to digest like “walking a mile in someone else’s shoes.” I just wish that my mother had this same opportunity throughout her lifetime to talk with others sharing the same fate instead of feeling so isolated and alone like she did.

As the CSN has grown over the years, many of the members determined to make a difference worked diligently to form a foundation called the International Cystinuria Foundation (ICF).  This foundation has developed a great deal of attention not only to many cystinurics but also many in the medical community who are interested in knowing more about this rare disease process.  Dr. David Goldfarb, a Nephrologist at St. Vincents Hospital in New York and a Professor at NYU serves as the groups’ medical panel and is kind enough to take his time not only to help educate and support this foundation but also do research as well to help better understand and possibly lead us to better treatment and a cure.

As a result of the ICF being formed, Dr. David Goldfarb along with many of his colleagues obtained accreditation to form a research consortia, The Hereditary Causes of Nephrolithiasis and Renal Failure.  On October 5th 2009, the NIH announced they would be expanding their rare disease research network awarding $117 million to 19 existing consortia, one of which is involves the direct research on Cystinuria (Dr. Goldfarb’s consortia).

Only one year later on October 15th 2010, the researchers with this grant published a demonstration of a chemical inhibition of cystine crystal growth in a most prominent and respected academic journal, Science.  This news has been amazing and celebrated not only by us but by all cystinurics  in that they may be getting closer to finding a way to limit or prevent the formation of cystine kidney stones.

As for today, I continually gather my own information everyday about this dreaded disease while supporting my children and keeping them healthy.  I do just try and stay focused on today, the here and now.  Luckily, I am blessed with an absolutely wonderful husband, a loving family, and supportive friends who are always by my side.

Sure my life has changed drastically over the past eight years but I will actually have to say it is for the better.  I look at everything differently now.  Trivial, frivolous events don’t enter my thoughts much anymore.  I seem to find myself more appreciative of simple little pleasures just as my kids do.  Enjoying every moment spent with my children is the most rewarding for me.  I also look at things from a positive aspect now.  For example, my children are probably the best behaved, most adaptable, easy going kids around.  I contribute this to Cystinuria. They tend to enjoy life more when they are feeling well and have less to complain about than others when the disease gives them a break from pain.

If Cystinuria is what was handed to me to take on for my children, then this is what I must do.  Continually informing the uninformed medical community and public through my experiences is a goal I am striving for in expectation of helping my children and other cystinurics.

I see my life now not just as a time span but as a quality of my existence.  I possess great goals now for my time here on Earth and what God has handed me.  If I may quote a fellow cystinuric from the CSN,  “My kids were born with a defect.  Like an automobile with a faulty transmission.  The only difference is that there are no recalls!”  So knowing this, we must accept the situation that is intended for us and do the best we can. Hopefully, even someday, beat it!