Christian M.

Christian M. – updated Febrary 2019

Christian M.

Christian M.

Christian, also known as CJ, is a fun loving five year old. He loves to listen to music, dance, and sing. His favorite activities include playing with his sister and watching YouTube videos. Christian is in full day kindergarten and loves socializing with his friends. Christian joined Yoga Club at school and he participates in gymnastics, tennis, magic classes, and horseback riding through the park district. He loves to travel and his favorite place to visit is the Great Smoky Mountains.

Christian’s older sister was diagnosed with Propionic Acidemia through the newborn prescreening, therefore we had a crisis management plan put in place for his birth. Within 48 hours of his birth, we received his diagnosis of PA. Currently, Christian eats 11 grams of protein, drinks Propimex-2, and take vitamins daily. We always seem to end up in the hospital during flu season, but other than that Christian has been a very happy and healthy little boy meeting all of his milestones.

Past story –  Christian – age 3


Christian M.

Christian, also known as CJ, is a three year old dancing machine. He loves to listen to music and have dance parties in our kitchen and basement. He is the life of the party and always making people smile. CJ attend preschool twice a week and is also involved in soccer and gymnastics. At home, he loves to follow his older sister around and try to play whatever she is playing. His superhero toys are often battling Barbies. Like most other three year olds, CJ loves cars, trucks, and his favorite television show is Paw Patrol.


Maya M.

Maya M. – updated February 2019

Maya M.

Maya M.

Maya is a nine-year old sweetheart. She loves watching YouTube videos and making her own videos for her MayaTV channel. Maya loves to make slime and listen to music on her iPod. She also likes traveling and going on vacation with her family. Maya is in third grade and loves reading, writing in cursive, and solving multiplication problems. She joined her Service Learning Club at school and participates in gymnastics, magic classes, tennis, drama, and horseback riding through the park district.

Maya was diagnosed with Propionic Acidemia after coming home from the hospital. We were fortunate to have a quick diagnosis through the newborn prescreening and avoided any metabolic crisis. Maya consumes 13 grams of protein by mouth daily. She drinks Propimex-2 and takes vitamins. Overall, Maya is a happy and healthy little girl who makes everyone smile with her humorous personality.

Maya – 7 years old

Maya M.

Maya M.

Maya is a seven year old, energetic, and hilarious little girl. She is currently in first grade where her favorite subjects are computer class and gym class. Maya loves to travel. Her favorite travel locations are anything involving a beach and sunshine. She spends basically her whole summer at her grandparents’ Yogi Bear campground. She loves “driving the golf cart”, swimming, fishing, and trying to catch frogs. Maya loves to try all activities. She has been involved in ballet, hip hop and tap classes. She has been in Lego club, Mad Scientist club, Cooking club, and Art club. She has also tried gymnastics and theater. Maya’s favorite hobbies include making videos of herself and playing with all of her baby dolls.

Maya was diagnosed with Propionic Acidemia through her newborn prescreening. With early detection, we were able to avoid any major crisis. Currently Maya consumes 13 grams of protein by mouth and drinks Propimex-2 daily. She is not a big fan of all her doctor’s appointments, but understands she needs them to stay healthy.


NIH PA Study

Natural History, Physiology, Microbiome and Biochemistry Studies of Propionic Acidemia

Charles Venditti MD PhD

Oleg Shchelochkov MD

National Institutes of Health

Why are we doing this study?

Propionic acidemia (PA) is one of the most common disorders of organic acid metabolism. Newborn screening for propionic acidemia allows doctors start treatment at an early age. However, despite early and intense medical treatment, many patients experience health problems. Patients can have frequent hospitalizations for metabolic crises and develop chronic medical issues such as brain, eye, heart, abdomen, and kidney problems.

To help better understand the health problems patients with propionic acidemia have, we are starting a new study: “Natural History, Physiology, Microbiome and Biochemistry Studies of Propionic Acidemia.” This study will evaluate patients with propionic acidemia to learn more about the genetic and biochemical causes and the medical complications associated with it.  We also plan to study how bacteria living in our gut (microbiome) can affect the course of propionic acidemia.

How can patients participate in this study and what will happen during the visit?

Eligible patients will be admitted to the NIH Clinical Center for 3-5 days. Most travel expenses are covered for patients and their care providers. A typical visit will involve a medical interview, physical examination, genetic counseling and consultation with experts in different fields, such as the nervous system, nutrition, rehabilitation medicine and other areas of medicine. Patients will be asked to provide blood, urine and stool samples to help measure function of organs affected by propionic acidemia. We use imaging studies such as X-ray and ultrasound to look for changes in organs inside the body. We may offer additional tests to some patients.

How can I find out more about this study?

You can find our more about this study by visit our the Propionic Acidemia Clinical Trials webpage

Contact information

If you are interested in learning more about the study please contact us:

[email protected]


NIH Clinical Center Patient Recruitment and Public Liaison Office



Scarlett Camille

Scarlett Camille   4/5/2006-11/21/09

The most wonderful thing in the world happened on April 5th, 2006 … you were born….Scarlett Camille.

scarlettSince then life was changed forever in a very special way!

There’s so many things you brought to my life, endless wonders, incredible sweetness, such a tiny little miracle child, unforgettable moments, joy that grew and grew, more love than you could ever dream possible!

I will never forget your strength and courage, and I will be forever proud to have had such a darling daughter.

Although your time here was short, you filled my heart with a lifetime of memories.

What a treasure, a touch of heaven here on earth.

Mommy’s little angel…

Awaiting the touch of a little hand and a smile from a little face.
Love you Bunny Bunny Bunny*

Reprinted from Autumn 2010 Newsletter




Article from Spring 2013 Newsletter

When people ask me about my brother it’s impossible NOT to smile.  He is such an amazing person!  He’s friendly, strong, funny and has an infectious laugh.  Reuben is completely comfortable being himself.  He doesn’t judge others and has the purest soul I’ve ever met.   It doesn’t bother me that he can’t drive, that sometimes I have to “translate” what he’s saying to others, or that everything in his world is related to a sport’s team- that’s “Rube”, my baby brother and my best friend.

I remember the day he was born very clearly, I was five years old and I was nervous, very anxious to meet what I thought would be a little sister.  I remember being ushered into the room with my grandparents and my mama had the bow on the newborn cap covered up with her hand and then FINALLY she unveiled it and my life was forever changed- Reuben Wade Kleckley was born March 22nd, 1984.  He was named after four generations of Kleckley men and I’m sure my parents had dreams of him playing professional baseball like my daddy and granddaddy did, but God had bigger plans for him.

When Reuben was two days old, he became very ill.  He was having seizures and went into a coma- and the doctors really couldn’t tell my parents why this was happening or what was wrong.  No one had any answers and I remember it was a very confusing time for me because what was a happy occasion quickly became a scary time for our family.  Once he was moved to ICU, I wasn’t allowed to see him because no children were allowed, and that was hard because as a new big sister that’s all I wanted to do.  After a few days, the nurses and my mom got together and broke the rules- dressing me in scrubs from head to toe so that I could hold him.  I remember his baptism and watching him being baptized in ICU with my baptismal gown on, wires all over and a specimen cup taped to side of his head so he wouldn’t pull out his IV again- he was such a pitiful little sight.  When Reuben was about a week old, he was flown to Johns Hopkins in Baltimore and was diagnosed with Propionic Acidemia, at the time there were only about 75 cases in the country so the doctors really didn’t give my parents a lot of hope.  Most children didn’t live past infancy and those who did, typically had significant developmental delays.  The latter proved true for Reuben.

As a child, in those first years I don’t think I really noticed that he had global delays- not walking until he was two or using phrases until he was four.  It never dawned on me that he wasn’t doing things like other toddlers, I was just happy he was with us since there were so many times he almost wasn’t.  I think we were more focused on his health with surgeries and trips to Duke to see specialists than any delays.  I know my parents knew early on that he was going to have challenges, but it took me awhile before I noticed he was different.  I remember the questions from friends and family and sometimes the stares when we would go out in public- it made me angry as a child, but it never made me angry at Reuben, it made me angry at the ignorance or other people.  The only thing that bothered me about growing up with a special needs brother was that it was very isolating, I didn’t know anyone else like me and I didn’t have any friends who understood.  I had no one to talk to about it.  My parents would try, but I was afraid of feeling or saying anything that might hurt them or make them worry.

I think the question I get asked most often is, “Do you ever wish your brother was normal?”  Sometimes people are shocked when I say “no”.  I mean, what is “normal”?  I think about how happy Reuben is, how much he enjoys the simple things in life and how, at 28, he is completely unaware of the negativity in this world.  He’s had a lot of struggles, but he’s had so many more positive experiences!  Having a sibling with special needs is not something you wish for and it’s not always easy, but Reuben has given us so much more than we could ever hope to give him. Christmas mornings are still exciting, watching him sing “Victory in Jesus” always brings tears to my eyes and it’s because of him that I’ve dedicated my professional career to working with children with special needs.

For a long time I’d heard “you’re so good with Reuben”… so, my family wasn’t surprised when I changed majors my junior year at USC, to work with children with disabilities.  Once I met my first child with autism, I was officially hooked.  I became an Early Interventionist after graduating in 2003 and in November, 2011, I partnered with a colleague to form Carolina Behavior & Beyond.  Our company provides early intervention services to children with disabilities and developmental delays, mainly serving children from birth to age five.   I love what I do and it’s truly amazing to see a child develop and transform before my very eyes.  I found my purpose in life and I know without a doubt, I have Reuben to thank for that.  He’s taught me that being different is not the end of the world, that there is wealth in every life if you have the heart to find it, and that you don’t have to be in the big leagues to pitch a no-hitter.

Update on Reuben!

Ace Right-hander was written in 1992 for a creative writing class I was taking at the time

Reuben will be 40 on his next birthday so it's probably time for an update. He's been very healthy since March 2020. Reuben attends a day program four days a week and a half-day program at our church, once a week.

He loves all things baseball and NFL football. Over the course of many Christmas's and birthdays he's accumulated almost all the team jerseys and hats. We know he's upset about something, which rarely happens, when he throws his hat. Reuben plays on a special needs baseball and basketball team and he loves bluegrass music in all its forms.

To live with Reuben is to be greeted in the morning with "Bless you Mom". His laughter can come for any reason or no reason at all and is as infectious as the common cold. He loves going to church and out to a restaurant, even though he probably won't eat anything, he just loves being around people. Reuben has been assigned the position of is Happiness Co-Ordinator at his sisters' Early Intervention company and is the primary reason she chose to work with children with special needs.

He is tube-fed all his nutrition, a mixture of Duocal, Anamix and Ensure and will snack on chips or Cheetos.

He has taught me so much about patience and enjoying the little things in life and being satisfied with whatever

comes our way.

Please feel free to contact me if you'd like to talk about our kiddos. I can be reached at



Propionic Acidemia Genetics Part 1

PA Genetics, Part 1


Propionic Acidemia (PA) is a condition caused by changes in the genes that make the propionyl-coenzyme A (CoA) carboxylase enzyme. Genes are made of DNA which is our hereditary material. Genes have the instructions that tell our bodies how to grow and function. Each gene provides specific instructions for various biological processes in the body.


The genes that make the propionyl CoA carboxylase enzyme are called PCCA and PCCB. The enzyme helps break down certain proteins and fats from food to make into chemical energy and other products the body needs. When there is a change in the gene called a mutation, the genes cannot perform their normal function.  If these genes do not work and the body cannot break down fats and proteins, there is a buildup of organic acids in the body which can cause the symptoms associated with PA such as vomiting, weak muscle tone, and developmental delays.


If someone has a mutation, it is something he or she was born with. These mutations happen randomly and they are not caused by something the person did. We have two copies of each gene. We inherit one copy from each parent. If someone has one gene with a mutation and one gene that works properly, they are called a carrier. Carriers do not have symptoms of propionic acidemia because having one working gene copy means the body is still able to break down fats and proteins.


If both parents are carriers of propionic acidemia, there is a 1 in 4 or 25% chance of having a child with propionic acidemia. This is called autosomal recessive inheritance.  The condition can affect males and females and an individual has to inherit two mutated genes to be affected with PA.  Therefore, in order to be affected by PA, the child has to inherit a gene mutation from both parents. If a child inherits one working gene and one mutated gene, they will also be a carrier of

PA and will not have symptoms.  If a child inherits both normal copies of

the gene, they will not be a carrier and not have the condition.



To find out if you are a carrier of PA, you can have genetic testing. Our DNA is written in a four-letter code. Genetic testing works by reading through the code like a spellchecker looking for a change, also called a mutation.


Robyn Hylind

Genetic Counseling Student

Northwestern University

Graduate Program in Genetic Counseling



Gwen M. – updated May 2015
My beautiful girl just turned 9 years old this year and it seems nothing short of a miracle. At 2 days of age, Gwen became catastrophically ill, her body temperature dropped below 90 degrees, ammonia level exceeded 1,500 umol/L and she stopped breathing. She was placed on a ventilator and received peritoneal dialysis for a couple of days until she came out of her coma and was breathing on her own. On her 3rd day she was diagnosed Propionic Acidemia and her future was very uncertain. During Gwen’s first 3 years of life she spent as much time in the hospital as she did at home. Although she’s been admitted more than 50 times, she’s undoubtedly one of the happiest people on Earth. At age 1 she stopped eating by mouth, and since then she’s been fed 100% by a feeding tube because she refuses to eat anything. For many years she wore a backpack to carry her feeding pump, but she is now able to tolerate her formula through small bolus feedings and has a nurse who cares for her during the day.Gwen knows she’s very cute and she plays that to her advantage. What she does not yet know is that she’s very brave, has an endless capacity to forgive, an amazing will to live, and a beautiful spirit from God that has touched the lives of hundreds. She talks non-stop, sings the entire time we’re in the car, jumps off of anything she can climb on, loves to dance, play with her American Girl dolls and spend time with her brother and friends. She’s in second grade and receives special education services for PT, OT, math and reading. She’s also in Brownies and on the Special Olympics swim team! She is a miracle, a daily blessing, and a ray of sunshine in any room. I am grateful for every day I have with her and so proud to be her mom.


Gwendolyn Grace M. was born at 3:33 p.m. on February 3, 2006. She will soon be only 5 months old, but has already brought a lot of drama to our lives! She was diagnosed at 3 days of age with Propionic Acidemia. At 2 days of life we found ourselves at Columbus Children’s Hospital emergency room only hours after being discharged from the hospital of her birth. We were quickly transferred to the NICU, where we spent the next 2 weeks. That first night at Children’s, her ammonia level reached over 1,500 & she had stopped breathing. The fantastic medical staff acted very quickly. Gwen was intubated & put on dialysis. We nearly lost her a couple of times during that stay, but she pulled through. She ended up having another episode less than 2 weeks after being discharged. Once again, she pulled through magnificently. We have quickly learned the fragile nature of good health, the strength of a family, along with the amazing power of prayer. My baby girl is nearly 4 months old & seems to be beating all the odds. Despite her rough beginning, she is meeting all her early milestones. Gwen has an awesome fun club, including her brother, parents, grandparents, aunts, uncles, cousins, doctors, nurses, teachers, & friends. We are so grateful for their love & support.   Check out our new web-site with even more pictures – Click Here.

Gwen’s 1st B-day!!!!

Dylan J

Dylan J |  Propionic Acidemia  |  Age 2 1/2

Dylan  J was born on October 12th, 2013 in Waconia, Minnesota, weighing in at 8 pounds, 2 ounces.  After Dylan was born, the doctors noticed that he had a lower than average body temperature, so they brought him back to the nursery to warm him up.  He was brought back to us, and from there on out for two days, we experienced a normal, healthy little boy, or so we thought.

In the early morning hours on October 15th, only 15 hours since we had been discharged from the hospital as a family of 3, Dylan was acting kind of strange.  He was very sleepy, and seemed cold to the touch.  My husband, Adam, and I took his temperature and he was at 95 degrees.  Knowing that wasn’t normal, I called my sister- in- law, who is a NICU nurse here in the cities, and she told us to try doing skin-on-skin to warm him up, and if that didn’t work, to probably call the on-call pediatrician.  Much to our dismay, an hour passed and he hadn’t warmed up at all, even after everything we had tried.  I called the on-call pediatrician and he told us to watch him over the next several hours, if he was still cold and was still very lethargic and didn’t want to eat, we could wait to bring him to the pediatrician office that opened at 8am that morning, or we could bring him to the emergency room.  About an hour later, my husband picked Dylan up to bring him to me to try and feed, and his arms fell limply behind his body.  It’s an image that is burned into my mind.  We knew at that moment something was wrong, so we packed him up in his car seat and drove him to the emergency room.  Once there, they looked him over, and told us that since babies can’t tell us what’s wrong, they would need to do many blood tests and a spinal tap to narrow down what was going on.  I remember the ER doctor telling us it was hard to watch little babies get pricked so he told us to go wait in another room (little did I know I would witness far more worse that these pokes in Dylan’s life to come).  Dylan’s breathing also started to become extremely  labored, he was really trying hard to get each breath in and out.  I don’t remember how long we were in the room, but I do remember the doctor coming and telling my husband and I, they didn’t have any results back yet, but they believed he needed to be transferred to a Children’s hospital in downtown Minneapolis, to put him on a ventilator, because he was getting too exhausted from working so hard to breathe.  He left the room, and I lost it, a ventilator, for my little baby?  What was wrong?  Later the doctor came back and said, he actually believed they might be able to just try oxygen, so they were transferring him upstairs, to their NICU, to see if we could get it under control.

It was then, that the waiting game began.  They did multiple blood tests, at one point coming to the conclusion that he was just dehydrated.  His blood sugar was very low, and they believed he just hadn’t eaten enough.  Hours passed by, and we were waiting for the neonatologist that did his rounds around the more suburban hospitals, to arrive and look at Dylan.  Around lunch time, the doctor came in and looked at him and told us he believed Dylan still needed to be transferred to the Children’s hospital to be put on a ventilator because the oxygen itself was not cutting it.  As he was telling us this, a nurse walked in, handed him a piece of paper, to which he looked at, replied “oh my gosh”, and left the room.  We were freaked out, but didn’t think too much of it.  Minutes later he came back in and told us that Dylan’s ammonia level was 900.  He looked at our very confused faces and told us that this was very, very serious, that the normal range was 10-35, and that Dylan may not make it.  I remember being numb, to the idea that my brand new baby could die, when an hour earlier we had just thought he was dehydrated.  The doctor left to set up an ambulance to take Dylan, not to the Children’s hospital anymore, but to the University of Minnesota Children’s hospital, because he needed special treatment, only available at the University.  He needed to be placed on Dialysis.

I rode in the ambulance with Dylan, and those were the longest 45 minutes of my life.  I remember thinking he was going to die in the ambulance, that there was nothing I could do, I just had to sit up in the front seat and pray.  Once we arrived at the hospital, it was like a scene out of a movie, all these doctors swarmed us, telling me they’d been waiting, explaining what was going on, needing me to sign consent forms to start dialysis.  Telling me that doing dialysis on a 3 day old baby was very risky, but what other choice did we have?  By the time we arrived at the hospital his ammonia had climbed to 1200.  My husband and I, and our families, were ushered into the family waiting room where we waited to hear word on Dylan.  It was at this time we were introduced to our metabolic doctor.  She came and met with us and described what she believed Dylan had.  A rare genetic disorder, where he could not break down protein correctly, and instead of breaking it down, he would only break down to a certain point and then the bad things (propionic acid and ammonia), would back up in his system.  With it being as high as it was, it was poisoning his organs.  They told us they believed his brain was swollen and they couldn’t be sure what brain damage he had received from the high ammonia, they would take ultrasounds and an MRI, which both came out fairly good, but really time would tell.

Many hours later, dialysis began, and a nurse came in, and said the words, I will never forget “I know this has been the worst day of your life, but I wanted to give you some good news, Dylan’s ammonia is 90”!  As fast as he got sick, he got better just as quickly.  They were able to rush Dylan’s newborn screening results and that confirmed his diagnosis of Propionic Acidemia.  The doctors now had a diagnosis and were able to treat him.  As the days passed in the ICU, his ammonia stabilized, they were able to start him on a low protein diet of Propimex and breast milk, and he did really well.  We were able to go home after just 7 days in the ICU.

Life with Dylan after that seemed to go very well, and to us was “normal”.  He was a good eater, always ate the amount of protein and calories he needed to get in a day and was developing normally.  I would check his ketones in his urine daily (our doctors thought I was a little crazy for checking so much, but it was my indicator something was off), and they were always negative until he was about 5 months old.  Dylan started getting trace to small ketones in his urine almost daily.  We would try to push more fluids, but they would still go back up.  He was eating all of his bottles very well still and acting completely normal.  However, once we saw ketones, we would bring him in to the emergency room and his ammonia would be high, in the 100’s.  The scariest part was, he never acted different, never showed signs his ammonia was high, except for the ketones.

After being in and out of the hospital for weeks at a time between February and May, our metabolic doctors decided to start him on Carbaglu, to help keep his ammonia in check.  When we were discharged from the hospital in late April after starting Carbaglu, we met for a follow up appointment with our metabolic doctors.  It was at this appointment that Dylan’s doctor sat us down and told us she believed Dylan needed a liver transplant.  You see, they were never able to tell us for certain if Dylan had a more severe case of PA or not, because after genetic testing was done, it came back that both of his mutations had never been seen before.  So we kind of had to wait and see how he did.  We were shocked, never had we thought liver transplant would be something we would be discussing for Dylan.  My husband and I went home and for a few weeks thought about it, prayed about it, cried about it, researched it, got stories from other parents that had gone through this, and ultimately decided that we didn’t want to wait until another crisis happened to Dylan and he had brain damage or worse, we wanted Dylan to remain Dylan.  So on May 8th of this year, when Dylan was 7 months old, we placed Dylan on the transplant list to get a new liver.

On July 24th, we got the call that they had a new liver for Dylan.  We dropped what we were doing and raced to the hospital where they did all the pre-surgery prep work, prepared us, and waited for word as to when the organ would be in Minnesota and when surgery would start.  On July 26th, the surgery happened.  My husband and I walked Dylan down to the pre-op room and handed him over to the transplant team.  We were guided to the family waiting room where we waited with our families for 8 very long hours.  When the surgeon came out, with a smile on his face, and told us it had gone very well, it was such a relief.  We were taken up to the PICU where we were able to see Dylan, and as scared as I was to see him, when we did, he looked so good.  Yes, he was hooked up to so many tubes and lines, and he was swollen, but he looked just like our boy.  We stayed in the hospital for 18 days as Dylan recovered.  His body accepted the new liver very well, and one of the best moments of our lives, was when our metabolic doctor came in and told us that the organic acid tests they had taken on Dylan after surgery had shown he had no propionic acid in his body!  What a miracle.

It’s been almost 2 years since Dylan has had his transplant and he is doing fantastic.  He’s had a few complications since but he’s gotten through them with flying colors.   Dylan will be on anti-rejection medications his whole life.  There’s the fear that he may go into rejection at any time, but if caught early enough, it is very treatable.  And here in Minnesota, with our doctors, they will keep a very close eye on him.  We also don’t have much research on if this liver will last his whole life, or if he would need a new one eventually, but at the same time, we don’t have a ton of data on what PA does to the body long term.  Our metabolic doctors are being very cautious with him, they kept him on his metabolic formula just until this last October when we tried to see what his labs did if he went off it and so far he has remained stable.  He is still on a restricted protein diet, right now he gets 30-35g a day.  The change in him since transplant has been tenfold.  Before he had low tone and now his tone is so much better, he runs and climbs just like every other 2 ½ year old when we’re playing at the park!  Although it was the toughest decision my husband and I have ever made, this was the right decision for us, we wanted Dylan to lead the best life he could, and even though there were so many risks, and we don’t know 100% what the future will hold, it was worth it, because he is such a happy and very healthy 2 ½ year old little boy!

Dr. Miyazaki

Dr. Toru Miyazaki, M.D.,Ph.D.                                              

The University of Texas Southwestern Medical Center  Dallas, Texas

Prior to becoming a 501(c)3, the PAF established a Propionic Acidemia Fund at UT Southwestern Medical Center in Dallas, Texas to promote the studies of Dr. Toru Miyazaki. With PAF’s help, this fund raised over $90,000. Dr. Miyazaki has succeeded in constructing a mutant mouse model of PA. The construction of this mouse model is significant because scientists now have a valuable tool to observe PA gene manipulation in an animal with propionic acidemia. This allows researchers to evaluate the function of genes transferred into the animal and to see how the body responds. Experiments in mice must precede human clinical trials involving gene therapy, so it is extremely important for this research to be performed.

Two genes, PCCA and PCCB are necessary for the production of propionyl-CoA carboxylase (PCC) an enzyme involved in the metabolism of the amino acids methionine, threonine, isoleucine and valine. Dr. Miyazaki’s mouse model contains a mutation in PCCA and these mice are unable to make PCC. PA mutant mice exhibit symptoms of propionic acidemia similar to human PA patients including poor feeding, dehydration and accelerated ketosis progressing towards death.

Dr. Miyazaki has confirmed that supplementation of 15-20% PCC (propionyl-CoA carboxylase) enzyme activity via a transgene to PA mice resulted in abolishment of most PA symptoms. Treated mice were able to consume a normal diet containing a high level of protein. Additionally they grew and developed like normal mice, procreated and lived a normal lifespan.

There is currently no research being done at UT Southwestern on Propionic Acidemia.   Those interested in reading more about Dr. Miyazaki’s studies may visit the sites below.

Dr. Barry August 2006 Progress Update

Michael A. Barry

August 2006 Progress Update from PAF Newsletter

The Barry Laboratory at the Mayo Clinic is working on a project to test if gene therapy can be used to treat propionic acidemia.  To test this, PA mice from Dr. Miyazaki are being used as subjects for delivery of the PCCA gene to their livers.  Sean Hofherr, a graduate student in Dr. Barry’s laboratory is pursuing this project for his Ph.D. thesis.  To date, Sean has generated a series of gene therapy vectors expressing either the human or the mouse PCCA gene for testing in the PA mice.  Preliminary experiments in the mice indicate that the vectors can be used to deliver PCCA gene to the liver to express amplified amounts of the protein.  Work is underway to determine how this modifies the blood levels of propionate metabolites and to what degree this rescues the whole body and neurological symptoms of the disease in the mice.   In the process of this work, Dr. Barry’s group generated antibodies against different parts of the PCCA protein to help in tracking where, when, and how much of the PCCA protein was being produced by their gene therapy vectors.  With these tools in hand, as a side project, their group has also used them to probe some of the basic biology of the PCCA protein.  While much is known about the genetics and disease symptoms of PA, little data can be found in the literature regarding the distribution of PCCA protein in different tissues.  For example, the level of protein expression in different tissues may explain (in part) some of the tissue damage and symptoms due to loss of PCCA.  Likewise, knowing where PCCA is and is not expressed might better guide how transplantation and gene therapies need to be applied and how this might differ between a mouse model and humans.  For example, one might predict that the liver expresses the highest level of PCCA given its role in metabolizing excess amino acids and fatty acids.  Conversely, one might predict that the brain or the basal ganglion might express lower amounts of PCCA, since many of the symptoms of the disease are manifested in these sites, particularly if these are due to effects within individual cells rather than due to metabolite overload.   Given these issues, Dr. Barry’s group used these new antibodies to screen for PCCA protein production in mouse and human tissue panels.  While they expected PCCA to be either ubiquitously expressed or expressed at highest levels in the liver, to their surprise, they observed a marked variation in amount of PCCA in different tissues.  In both mouse and human tissues, the kidney appeared to have the highest levels of PCCA protein, in fact higher than in the liver per unit protein.  In contrast, in the brain, PCCA was undetected in mouse (but not necessarily zero), and was detectable, but at low levels in the human brain samples.   These data suggest PCCA is not ubiquitously expressed at high levels in all tissues and that the kidney may play a significant role in elimination of propionic metabolites.  While the kidney had higher levels of PCCA when equalized for protein in the different tissues, it should be noted that the liver is still substantially larger in size and so likely  “handles” substantially more metabolites.  However, better knowledge of the locations of PCCA and cross-talk between organs may assist in optimizing therapeutics and to avoid mis-steps when translating between mouse models and PA patients.  Work is underway to screen more specific regions of the brain for PCCA expression and to track how the protein’s expression may change over time in the PCCA mutant mice.