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A support group for families living with methylmalonic, propionic, isovaleric, and other organic acidemias Organic Acidemia Association 9040 Duluth Street Golden Valley, MN 55427 Phone: 763.559.1797 Fax 866-539-4060 www.oaanews.org Kathy Stagni, Executive Director Propionic Acidemia parent 9040 Duluth Street Golden Valley, MN 55427 Phone: 763.559.1797 [email protected] Menta Pitre, Director MMA Cbl C Parent 207 E. 14th PL Larose LA 70373 Phone: 985.856.5631 [email protected] Cay Welch, Director Glutaric Acidemia, Type 1 parent P.O. Box 427 Ridgway, CO 81432 Phone: 970.316.1780 [email protected] Jana Monaco, Advocacy Liaison Isovaleric Acidemia parent 3175 Ironhorse Dr. Woodbridge, VA, 22192 Phone: 703.497.1216 [email protected] Happy Holidays! Jana Monaco and I had the opportunity to attend NORD’s Rare Disease Summit in October in Arlington, VA. Jana was invited to speak on a panel regarding newborn screening. I was fortunate to receive a scholarship from NORD for registration and travel. It was so exciting to hear how much our rare disorders have progressed in regard to treatment and diagnosing. Here is a link to the agenda and some of the presentations - http://www.cbinet.com/PC15215 I had the pleasure of speaking with two representatives from pharmaceutical companies who are actively working on cutting edge treatments for our disorders. One pharmaceutical company, Hemoshear produced a “TedTalk” and I invite you to listen the amazing possibilities for this new treatment. e link to this TedTalk on YouTube can be seen at this link: https://www.youtube.com/watch?v=bRfcmSD8goE&feature=youtu.be anks to those who have shared their stories in this issue of the newsletter. I’m happy to share the update from Dr. Manoli, Jennifer Sloan and Dr. Venditti at the NIH – New research studies caution against overuse of medical foods for patients with methylmalonic acidemia (MMA) and cobalamin C deficiency (cblC) can be relevant for other MMAs and Propionic Acidemia. Dr. Venditt’s team is doing amazing work on understanding more about our organic acidemia disorders. I have also included the registration form for the upcoming family conference. We have booked our hotel in Westminster, Colorado for Friday and Saturday, July 8&9. More information and agenda will be announced in the next newsletter and our Facebook group. I hope you all have a very blessed holiday season. Stay well! OAA Newsletter Family Stories Family Matching Family Conferences Research Funds Awarded National Advocate for Newborn Screening Parent Support, Education & Awareness www.oaanews.org IN THIS ISSUE NON-PROFIT TAX ID # 48-1038050 VOLUME: XXXII, ISSUE: 3 Financial Statement 3 Michael : Glutaric Acidemia, Type 1 4 Someone Special Books 5 Grady : Methlymalonic Acidemia, Cbl C 6 Registries and Research 7 Carter and Harper : Glutaric Acidemia, Type 1 8 Caution Against Overuse of Medical Foods 9 Epi-743 Update 12 Metabolic Conference Registration Form 13 In Memory : Jennifer Lynanne Mabbott 15
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Page 1: Happy Organic Acidemia Association Holidays · 2019. 10. 19. · A support group for families living with methylmalonic, propionic, isovaleric, and other organic acidemias. Organic

A support group for families living with methylmalonic, propionic, isovaleric, and other organic acidemias

Organic Acidemia Association 9040 Duluth Street

Golden Valley, MN 55427 Phone: 763.559.1797

Fax 866-539-4060 www.oaanews.org

Kathy Stagni, Executive Director

Propionic Acidemia parent 9040 Duluth Street

Golden Valley, MN 55427 Phone: 763.559.1797 [email protected]

Menta Pitre, Director MMA Cbl C Parent

207 E. 14th PL Larose LA 70373

Phone: 985.856.5631 [email protected]

Cay Welch, Director Glutaric Acidemia, Type 1 parent

P.O. Box 427 Ridgway, CO 81432 Phone: 970.316.1780 [email protected]

Jana Monaco, Advocacy Liaison

Isovaleric Acidemia parent 3175 Ironhorse Dr.

Woodbridge, VA, 22192 Phone: 703.497.1216

[email protected]

Happy Holidays!Jana Monaco and I had the opportunity to attend NORD’s Rare Disease Summit in October in Arlington, VA. Jana was invited to speak on a panel regarding

newborn screening. I was fortunate to receive a scholarship from NORD for registration and travel. It was so exciting to hear how much our rare disorders have progressed in regard to treatment and diagnosing. Here is a link to the agenda and some of the presentations - http://www.cbinet.com/PC15215 I had the pleasure of speaking with two representatives from pharmaceutical companies who are actively working on cutting edge treatments for our disorders. One pharmaceutical company, Hemoshear produced a “TedTalk” and I invite you to listen the amazing possibilities for this new treatment. The link to this TedTalk on YouTube can be seen at this link: https://www.youtube.com/watch?v=bRfcmSD8goE&feature=youtu.be

Thanks to those who have shared their stories in this issue of the newsletter. I’m happy to share the update from Dr. Manoli, Jennifer Sloan and Dr. Venditti at the NIH – New research studies caution against overuse of medical foods for patients with methylmalonic acidemia (MMA) and cobalamin C deficiency (cblC) can be relevant for other MMAs and Propionic Acidemia. Dr. Venditt’s team is doing amazing work on understanding more about our organic acidemia disorders.

I have also included the registration form for the upcoming family conference. We have booked our hotel in Westminster, Colorado for Friday and Saturday, July 8&9. More information and agenda will be announced in the next newsletter and our Facebook group. I hope you all have a very blessed holiday season. Stay well!

OAA Newsletter • Family Stories • Family Matching • Family Conferences • Research Funds Awarded • National Advocate for Newborn Screening

Parent Support, Education & Awareness www.oaanews.org

IN THIS ISSUE

NON-PROFIT TAX ID # 48-1038050 VOLUME: XXXII, ISSUE: 3

Financial Statement 3Michael : Glutaric Acidemia, Type 1 4Someone Special Books 5Grady : Methlymalonic Acidemia, Cbl C 6Registries and Research 7

Carter and Harper : Glutaric Acidemia, Type 1 8 Caution Against Overuse of Medical Foods 9 Epi-743 Update 12 Metabolic Conference Registration Form 13In Memory : Jennifer Lynanne Mabbott 15

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2 : OAANEWS.ORG

Medical Advisors

Dr. Olaf Bodamer FACMG Biochemical Genetics University of Miami

P.O. Box 019132 (M-860) Miami, FL 33101

Elaina Jurecki, MS, RD BioMarin Pharmaceutical Inc.

105 Digital Drive Novato, CA 94949

Keiko Ueda, MPH, RD, LDN Clinical Dietitian Specialist

Biochemical Diseases (Metabolism) Program British Columbia Children’s Hospital

4480 Oak Street, K3-211 Vancouver, BC V6H 3V4 Canada

Stephen Cederbaum, MD Mental Retardation Research Ctr./NPI 635

Charles E. Young Dr. South Rm 347 Los Angeles, CA 90095-7332

Stephen G. Kahler, MD Univ of Arkansas for Medical Sciences Clinical Genetics Division Slot 512-22

Arkansas Children’s Hospital 800 Marshall St.

Little Rock, AR 72202-3591

Charles P. Venditti MD, PhD Genetic Disease Research Branch

National Human Genome Research Institute National Institutes of Health Bldg 49,

Room 4A56A Bethesda, MD 20892-4472

Kimberly A. Chapman, MD, PhD, FACMG Assistant Professor of Pediatrics

Section of Genetics and Metabolism Children’s National Medical Center

111 Michigan Avenue, N.W. Washington, D.C. 20010

Piero Rinaldo, MD, PhD Biochemical Genetics Laboratory

Department of Laboratory Medicine Mayo Clinic

200 First Street SW Rochester MN 55905

Jerry Vockley, MD, PhD Professor of Human Genetics & Pediatrics

Chief of Medical Genetics Children’s Hospital of Pittsburgh 3705 Fifth Avenue Pittsburgh, PA

15213

Carla Cuthbert, PhD, FACMG, FCCMG Chief, Newborn Screening and Molecular

Biology Branch And the Newborn Screening Quality Assurance Program, Division of Laboratory Sciences, NCEH,Centers for

Disease Control and Prevention 4770 Buford Highway, MS-F43

Atlanta, GA. 30341

Mendel Tuchman, MD Professor of Pediatrics, Biochemistry &

Molecular Biology Children’s National Medical Center

111 Michigan Avenue, NW Washington, DC 20010-2970

Dr. Susan Winter, MD Valley Children’s Hospital

9300 Valley Children’s Place C/O Medical Genetics/Metabolism SE11

Madera, CA 93638

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DECEMBER 2015 : 3

In the fall of each year, after filing the annual 990 report with the IRS, the board of the OAA publishes the organization’s financial status. The statement shown recaps years 2014 and 2013.

The OAA ended the year with $54,454 in available funds, which reflects a decline of $3,531 from the previous year after all expenses were paid.

Contributions for the year included $38,500 in support of the 2014 National Family Conference. Non-conference contributions toward the operating and research funds totaled $37,652 which is down slightly from the amounts received in 2013 (our non-conference year).

Annual expenses, excluding the cost of the National Family Conference, totaled $20,913 which was an increase of $6,674 from the amount spent in 2013. This increase was primarily the result of the newsletter upgrade and staff travel expenses for attending national conferences representing the OAA. No research grant was made to the NIH in 2014.

On behalf of everyone associated with the OAA, we thank our financial contributors – because without their support we would not be able to deliver the services for parents and professionals that have become the hallmark of our organization since its founding over three decades ago.

OPENING FUND BALANCE FY 2014 FY 2013

OAA Operating Fund $ 52,471.00 $ 34,845.54

OAA Research Fund $ 5,514.00 $ 8,000.00

TOTAL $ 57,985.00 $ 42,845.54

CURRENT YEAR CONTRIBUTIONS & INTEREST

OAA Operating Fund $ 73,116.00 $ 31,865.00

OAA Research Fund $ 3,036.00 $ 7,514.00

TOTAL OAA $ 76,152.00 $ 39,379.00

PROGRAM EXPENSES

Newsletter $ 9,906.00 $ 6,101.54

National Family Conference $ 58,200.00 $0.00

Accounting Services $ 2,042.00 $ 1,350.00

Office, Internet, Phone, etc. $ 4,169.00 $ 2,814.00

Program Expenses $ 4,816.00 $ 3,974.00

TOTAL PROGRAM EXPENSES $ 79,133.00 $ 14,239.54

RESEARCH GRANT

National Institute of Health $ 0.00 $ 10,000.00

Childrens Hospital $ 550.00 $ 0.00

TOTAL GRANTS $ 5,500.00 $ 10,000.00

ENDING FUND BALANCE

OAA Operating Fund $ 46,454.00 $ 52,471.00

OAA Research Fund $ 8,000.00 $ 5,514.00

TOTAL $ 54,454.00 $ 57,985.00

NET CHANGE CURRENT YEAR -$ 3,531.00 $ 15,139.46

Financial Statement

The 2016 OAA Calendar Now Available

Support OAA by purchasing your calendar today! The calendar and other items can be purchased from OAA’s CafePress Store - www.cafepress.com/organicacidemiaassociation.

Thanks again to Raymonde, mom to Marc Antony, MMA Cbl C for creating our wonderful

2016 OAA calendar.

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M y name is Michael and I have Glutaric Acidemia type 1. I am in a power wheelchair which I drive with switches near my head. I

also have a communication device which I use to speak. I don’t let my disability stop me from doing the things I want to do.

There are many activities I do that may surprise you. Every winter, I go skiing with my family in Connecticut. They have an adaptive sleigh called a bi-ski which allows handicapped people to go down the mountain. I get strapped into the bi-ski and I have an instructor behind me who controls my speed. When I first started skiing, my instructor controlled my speed and turning. However, now that I have experience, I am able to control which way the ski goes by leaning left and right. Also, with many hours of practice, I have won 4 medals in the annual Stride Great Race at Jiminy Peak in Massachusetts.

Another thing I do is play chess. When I play, I tell somebody what piece I want to move and where I want it to go. I attend chess class every week and it has helped me win 3 chess tournaments. I also play flag football. The flags are attached to the back of my chair and I have a buddy who catches the ball and places in my lap, then I can run the ball down the field. When I am at home, I play video games. I have a giant adapted controller with big buttons and joysticks. There are multiple ways a handicapped person can use this controller. All of these activities are what I do for fun.

Now it’s time to talk about school. I started out at The Children’s Therapy Center when I was 3 years old. At the pre-k program, I not only learned my ABC’s but I received my therapies there as well. When it was time for kindergarten, my parents thought I would be better off mainstreamed because they knew I had the capacity to handle it. It was the best decision they made. It was challenging in the Fairlawn school district, but I managed to never get below a B in any class.

Now, I should tell you that I have a girlfriend. Yes, you read that right. I have a girlfriend. Her name is Sara and we have been dating for 3 years. She is also in a power chair and uses a communication device. We met at Camp Chatterbox. We visit with each other several times throughout the year and text just about every day.

That is everything I have experienced in my life so far. However, I have big plans for the future. I am trying to figure out what I want to do for a career, so currently I am taking general education courses at the community college. Finally, sometime in the near future, I want to go skydiving.

MICHAEL FAIR LAWN, NEW JERSEY | [email protected]

Michael : Glutaric Acidemia, Type 1 | Age 18

More about MichaelIt has been 12 years since our last update, so I will start with a brief history and then bring you up to date on our 18 year old son. Our son Michael was diagnosed with Glutaric Acidemia Type 1 when he was 8 months old. As a baby, he had low muscle tone and we were sent to a neurologist who did blood work and a urine test. The high level of glutaric acid in his urine was the first sign. After seeing a genetic specialist at Mt. Sinai in New York and having

a skin biopsy the diagnosis was confirmed and we started on the road to special formulas and diet. This meant being careful of childhood illnesses, hospitalizations for hydration when Michael was sick and constant monitoring of his protein intake. Michael had no crisis that we can pinpoint, other than a high fever during an ear infection prior to diagnosis, which may have caused the brain damage that he has, which affected his physical development. Michael is unable to walk or talk and has limited use of his hands. He uses a power wheelchair and a communication device to speak.

Soon after diagnosis we began doing some research on line, we were fortunate enough to find Dr. Morton at the Clinic for Special Children in Strasburg, PA. Early on we visited them several times a year for Michael’s metabolic care, while working with our pediatrician for all other typical medical care. Now that Michael is 18 years old, we visit once a year for a check-up, blood work and to update of his feeding plan.

In our last update, when Michael was six we spoke about how he struggled with eating and not gaining weight, this led us to having a feeding tube placed when he was seven years old. Michael continues to get the majority of his nutrition through the tube and eats some food by mouth. Overall, Michael is very healthy, very rarely gets sick and has not been hospitalized for illness since getting the feeding tube. He has had two surgeries: one to lengthen the tendons in his legs when he was eight years old: and in 2012, he had back surgery to place a rod in his back to straighten his spine.

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DECEMBER 2015 : 5

This 16 page picture book is designed to bring

about awareness and acceptance for children with

food allergies. The story functions for a wide range

of allergies; everything from a peanut allergy to severe

metabolic conditions. Many questions can arise in

young children about why their classmate can only

consume certain foods, and this story answers those

questions through colorful illustrations and kid-friendly language. It also teaches an important lesson about kids

not sharing snacks.

We create personalized picture books for children with special needs. Each book is designed to help children everywhere learn kindness, acceptance, confidence, and respect.

You will have the ability to personalize a book with the child’s name, a personal photo, a dedication message, birthday, four different hobbies or interests, and the name of their condition. The last page of the book is left blank to add any additional information about the child that may not have been covered in the book such as medications, specific behaviors, or personal stories.

This 16 page picture book is designed to bring about awareness and acceptance for children with food allergies. The story functions for a wide range of allergies; everything from a peanut allergy to severe metabolic conditions. Many questions can arise in young children about why their classmate can only consume certain foods, and this story answers those questions through colorful illustrations and kid-friendly language. It also teaches an important lesson about kids not sharing snacks.

For more information visit: Someonespecialbooks.com or email: [email protected]

Children with Organic Acid Disorders have a wide spectrum of needs. If the “food allergy” book is not appropriate, email us and we will help find a book to

meet your needs.

We realized very early on while Michael was in a special needs preschool that he was extremely intelligent, and were encouraged to mainstream Michael in our local school. We did mainstream Michael, not without some struggles, but

we are sure glad we did. Michael graduated last year and is now attending our local community college. In addition to school, Michael has many other interests and activities that he participates in to the best of his ability. I will not go any further, as I know he will be sharing that in the article he is writing for you.

Michael has a sister Julie (unaffected), who is 16 years old. They continue to be best friends, yet have their moments like any other brother and sister. We continue our journey raising a child, sorry, young man with GA1. It doesn’t necessarily get easier, just different. The challenges are different, the successes are just as rewarding and it is funny how this all just becomes normal.

LARRY & GRACE FAIR LAWN, NEW JERSEY

[email protected]

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M ay Day 2014 was one of the most exciting days of my life. I was exactly one

week overdue with my second child. We had a 22-month old daughter and were anxiously awaiting the arrival of our little boy to complete our perfect family. Our daughter Claire had been born early, and I was so excited that this time around I wouldn’t have the stress of caring for a small baby. All I could think of was how chubby he would be when I finally got to see him. After a smooth labor and delivery, my Grady David was here. He had 10 fingers, 10 toes, breathing, strong heartbeat, but he was small; not what I expected for an overdue baby.

The first couple days of life with Grady were so smooth. He nursed great, slept normal, and was mild tempered. His sister loved him already, and we felt blessed. Due to him being jaundice, I was instructed to nurse every 3 hours and then offer a bottle after each feeding to make sure he was getting enough fluids. Each feeding he nursed fine, but barely drank from the bottle. On day 4 of life he would start to nurse and fall asleep before finishing his feeding. Towards the end of the day, he would cry out of hunger, start nursing, and then immediately break his latch. The following day I dropped my daughter at daycare and went to my parents’ house to let 5-day-old Grady sleep in front of their big windows to help with the jaundice. My cell phone alarm woke me from a nap to feed Grady, but before

I could start our family doctor called. She asked how Grady was. I told her I was actually thinking about calling her that day because he was very sleepy and breaking his latch. Without responding to me, she started speaking to someone on another line, repeating my words. She instructed me to have someone drive us directly to NICU in Madison, and to feed him in the car. She said his newborn screen showed the presence of organic acids, and he needed to be seen by a metabolic specialist immediately.

Grady was admitted into the NICU for a 7-day stay where he started treatment. He was having trouble regulating his temperature and had some irregular breathing patterns. He continued to eat while there and eventually started nursing again. Grady was diagnosed with Methylmalonic Acidemia, and shortly after confirmed as being Cobalamin C. During his stay, we saw our first physical therapist where we heard the term “floppy”. He was arching constantly during those early days as well, and could almost roll on his own. We learned this was from his muscle imbalance and low muscle tone. He also had an MRI while in the NICU, which was normal.

Through the course of the next couple months we met with and developed Grady’s medical team and learned more about his disease and how it was affecting him. Looking back to my pregnancy, it was obvious he was being affected in utero. At 33 weeks my

doctor first started noticing slow growth. This trend continued, but multiple ultrasounds convinced us he was growing and healthy. Within the first couple months we met his cardiologist, who diagnosed Grady with cardiomyopathy. At the same time Grady’s heart rate was elevated, likely compensating for the lower function. Now, at 18 months, he has been given a clear cardiology report and his heart is functioning normal. His neurologist continues to monitor him, but feels he is developing normally. Vision issues are one of the most common, and devastating, effects of having Cobalamin C. He started seeing an ophthalmologist regularly monitor the health of his eyes. He has never shown any signs of nystagmus or strabismus, but does have retinal irregularities. Visually Evoked Potential (VEP) tests confirm lessened vision in his left eye, where the maculopathy is more pronounced. Although he has these vision issues, he plays, eats, and explores like a child that can see perfectly fine.

While we have since day one been very happy with Grady’s medical team, we felt something was missing in his treatment. He was extremely responsive to B12 early on. As he grew, his oral medications (betaine, levocarnitine, leucovorin, and Metanx) increased dosage with weight, but the B12 remained the same. As Grady gained weight, his levels started creeping up. We requested to have his B12 increased to follow weight as well, even though it was not the recommended amount for his age. Our

Grady : Methlymalonic Acidemia, Cbl C | 18 months

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DECEMBER 2015 : 7

geneticist agreed to see if it lowered his levels, which to our delight, it did. Although we were happy with the results, we wanted more and continued searching for articles that would indicate it was an option. When Grady was 3 ½ months old, a mom joined the Facebook support page and private messaged me about her son, just diagnosed with CblC. Through conversation with her I found out her son was on a very high dose of B12. Our doctor reached out to their geneticist to learn more about it. At 5 months old, Grady started the higher dose of B12 and his levels dropped almost in half. He had so much more energy and was overall much healthier.

I truly believe my son is the thriving, wild, little boy he is today because of the networking we found through online support groups and our geneticist’s openness to try new treatment. With rare disease, our role as parents is to be a researcher and figure out how we can help our children. Along with medicine, we found that therapies were very beneficial. Grady seemed to have tightness and pain as an infant from his muscle imbalance. Weekly trips to the chiropractor for pressure point therapy helped him sleep more comfortably and perform better in physical therapy. Grady has met all this major milestones, with physical therapy as a major contributor. By networking with other moms, I learned feeding techniques (thickening milk) that made drinking bottles easier for Grady. Although we didn’t have one, a speech therapist would have been helpful for feeding issues. I also highly recommend parents seek a case worker through their insurance company if possible. Dealing with insurance can be a full time job, and our case worker now deals with all the hassle for us and makes sure all of the requests are run through smoothly.

My most important advice I can give a parent new to this world is to find support. We have been blessed with an amazing family, who at the drop of a hat, helps in any way possible. Teaching our family about medications and care helped us not feel trapped by the disease. Online support networks have been my saving grace in so many ways. I have found my best friends through Facebook, whose children also have CblC. It’s an instant bond that can get you through the worst. For anyone in need of support, feel free to call, email, or text me any time.

When I think back to Grady’s diagnosis, I was heartbroken that he would miss out on all the dreams I had for him. Now, at a year and half, I see he’s not missing a beat. Life has its bumps, but he is going to do everything I dreamt for him, in his own way. I am in awe of my little man every day and all he brought to my life in 18 short months.

DANIELLE [email protected] | 608-341-7237

DODGEVILLE, WI

We all want what is best for our children, and ourselves but sometimes it is hard to determine what things, medications, or interventions (or schools or foods or therapies or…) that may be.

As a biochemical geneticist, I too want my patients to do well and thrive. But let us be honest, current therapies and treatments are not as good as we need them to be. Thus, I am a firm believer in participating in research. You as a patient, caregiver or parent can participate too.

There are a number of things we do not know about organic acidemias (and other metabolic diseases). These things are fairly basic like how common are these disorders, what interventions or therapies are used in different places, or what medications work or are used?

In partnership with National Organization for Rare Diseases (NORD), we will be rolling out a cloud based patient/family driven natural history study for organic acidemias in 2016. This information will be crucial to developing new therapies and making those we have more effective. We will need your input as we design what data to gather. I will keep you updated on our progress.

REGISTRIES AND RESEARCH

Kimberly A Chapman MD PhD, Children’s National, Washington DC

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8 : OAANEWS.ORG

H i there, my name is Amber and I am the proud mom of three beautiful children,

Carter, 10 (ga1), Callum, 6 (unaffected) and Harper is 3 (ga1). The last time I wrote for OAA, Carter was 2 and we had been through the ringer with his health issues. After a child abuse accusation and 3 surgeries to remove fluid and blood around his brain, he was finally diagnosed with GA1 at 13 months old. He is now 10 and doing extremely well! He excels at school, plays hockey, baseball and guitar, and has a great personality! He is on carnitine, and although we do not closely monitor his diet, he knows that he can only have a limited amount of protein and does great on managing it himself! The last time he was hospitalized he was five years old, and thankfully he has no memories of all of the needles and IV trauma. I think all of the hospital stays were harder on me than him!

We were so happy to welcome our second son in 2009, and to find out he was unaffected by GA1 was a huge relief! When Harper came in 2012, we were super excited to have a daughter, but I have to admit that we were devastated to discover her diagnoses. I thought about all of the hospital stays and needle pokes

with Carter, and I was sad that she would have to go through all of that. I was also worried about how I was going to protect her from getting sick with two older brothers bringing home germs from school? I was terrified, but thanks to the grace of God, she has only been hospitalized once during a stomach flu when she was 2 ½. She has somehow managed stay extremely healthy, or we have been able to keep her hydrated at home through illnesses. She is now on a similar care plan as Carter, but she does drink her Glutarade essential every day. She is very smart and is doing great developmentally, and she enjoys her ballet and swimming classes. I plan on enrolling her in preschool in the fall as well.

Raising children with GA1 has at times been extremely challenging, but we try not to make too big of a deal of it so that Carter and Harper don’t feel that they are different from others. At times Carter will comment that he wishes he didn’t have ga1 so he can eat lots of protein, but we just remind him that there are lots of people out there with health issues, and that he really is extremely blessed to be so healthy. It is nice for us to be out of the danger zone, now that our kids are older and passed the stage of being vulnerable to injury,

but I remember how scary it is to have an infant with GA1, and I want to send my love and encouragement to all of the parents out there who are living through those stressful times. I had no one to talk to when I was there, and would be happy to be there for anyone who needs it. Please do not hesitate to contact me with any questions, or even if you just want support or prayers from someone who has been there.

Thanks for reading!!

AMBER [email protected]

EDMONTON ALBERTA CANADA

780-973-3030

Carter and Harper : Glutaric Acidemia, Type 1 | Ages 10 and 3 years

JANUARY 20160AA CALENDAR

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DECEMBER 2015 : 9

Methylmalonic acidemia and cobalamin C deficiency (cblC) are rare genetic conditions in which the body cannot properly turn protein-containing food into energy. Patients with isolated methylmalonic acidemia (MMA) who have mut0/mut-, cblA or cblB deficiency cannot breakdown certain amino acids (specifically the amino acids valine, isoleucine, methionine and threonine), because the MUT enzyme does not work correctly. Patients with cblC cannot process vitamin B12 inside the cell, which affects the MUT reaction causing elevated plasma methylmalonic acid, but not as high as those with isolated methylmalonic acidemia. Patients with cblC also have impaired synthesis of methionine from homocysteine resulting in high homocysteine and low methionine concentrations in the plasma. Although often grouped together, isolated MMA and cblC are distinct conditions that require different management. Propionic acidemia (PA), on the other hand, is caused by an enzymatic block in the same pathway, therefore the same medical foods and very similar dietary guidelines are followed for both isolated MMA and PA patients.

“Medical foods” are special formulas designed to help manage patients with inborn errors of metabolism (IEMs), including various forms of methylmalonic acidemia. They are designed as a specially modified protein source, which instead of intact/whole protein contains free amino acids with the exception of the four “toxic” amino acids that MMA and PA patients cannot metabolize (valine, isoleucine, methionine and threonine). What makes dietary management in MMA/PA very challenging is that these “toxic” amino acids are essential; the body cannot make them and people must obtain them from food to support growth and brain development. One

cannot remove these essential amino acids from the diet altogether or the body will develop deficiencies that can cause serious health problems (poor growth, weight loss, decrease in muscle and bone mass, changes in hair, skin breakdown, fatigue, immune system dysfunction among other). Medical foods are therefore always prescribed in combination with intact/whole protein that supplies the essential amino acids for patients with MMA/PA.

The total amount of protein in the diet, as well as the balance between intact/whole and deficient/medical foods derived protein is a moving target throughout the lifetime of each patient with MMA/PA. In the metabolic clinic, the teams make assumptions based on a number of variables including the weight and age of the patient, the day-to-day needs depending on illness or other catabolic states (surgery, anesthesia, sepsis, other), catch-up growth requirements after a severe admission, growth spurts (puberty), the level of physical activity, and the baseline energy expenditure (which in turn can be influenced by hypothyroidism, low muscle mass, kidney disease, fever, and other individual variables). Frequent monitoring of the plasma amino acids, serum methylmalonic acid concentrations, and other metabolites, along with the continued monitoring of weight/height/head circumference are necessary to find the perfect balance for each patient during various periods of growth. The ultimate aim of dietary therapy is to provide each patient with a safe source of calories and nutrients that will help support their growth (height, weight, head circumference, muscle and bone mass) while reducing the accumulation of critical metabolites and the risk for disease-related complications.

Caution Against Overuse Of Medical Foods For Patients With Methylmalonic Acidemia (MMA) and Cobalamin C Deficiency (cblC)

CHARLES P. VENDITTI MD, PHD ORGANIC ACID RESEARCH SECTION

MEDICAL GENOMICS AND METABOLIC GENETICS BRANCH - NATIONAL HUMAN

GENOME RESEARCH INSTITUTE BETHESDA, MD 20892

EMAIL: [email protected]

[ CONTINUED NEXT PAGE ]

NEW RESEARCH STUDIES

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Through our ongoing natural history protocol at the National Institutes of Health Clinical Center in Bethesda, MD (clinicaltrials.gov identifier: NCT00078078), we have evaluated over 170 patients with different types of methylmalonic acidemia and cobalamin disorders between 2004-2015. In two studies published online August 13, 2015 and in the August issue of Genetics in Medicine, “A critical reappraisal of dietary practices in methylmalonic acidemia raises concerns about the safety of medical foods. Part 1: isolated methylmalonic acidemias and. Part 2: cobalamin C deficiency. “We reported our experience with dietary management of patients with isolated methylmalonic acidemias and cobalamin C deficiency. 61 patients with isolated MMA (46 mut, 9 cblA and 6 cblB) and 28 early-onset cblC patients contributed data for these studies. This is a much larger number of patients than any individual metabolic clinic can collect, necessary to perform comparisons and correlations between the diet and different outcome parameters in these rare disorders. Also, because patients participating in the NIH study came from many different metabolic clinics in the USA and different centers internationally (UK, Australia, South America, China), the cohort represented a diverse patient population, which allowed our team to collect data from patients treated by widely different practices.

Similar to what others and we had reported previously, patients with isolated MMA, including patients with mut0/mut-, cblA and cblB had poor long-term growth outcomes. In most patients, height, weight and head circumference were lower than average, while body mass index (BMI) and body fat percentage were higher. We had previously measured resting energy expenditure (a measure of how many calories a person’s body burns at rest) and showed that patients with mut MMA have lower than expected basic energy expenditure because of their chronic renal disease and low muscle mass. This means patients with isolated MMA are usually prescribed many more total calories than they need, which predisposes them to obesity. In this study we tried to investigate how dietary factors might contribute to their low height and how we could optimize nutrition to improve growth.

Another puzzling observation of our study was that a number of our patients were chronically deficient in the essential amino acids valine and isoleucine, requiring individual amino acid supplementation in form of valine and isoleucine syrup. This was completely paradoxical because these are the very same “toxic” amino acids that are turned into methylmalonic acid in the body, and precisely the ones we are trying to restrict in the diet. Moreover, some of the patients on the valine and isoleucine syrups were taking a generous amount of whole protein in addition to medical foods, so the reason why their valine and isoleucine levels were low was not immediately

apparent based on their dietary intake – i.e. they were not protein restricted.

This led us to systematically review each patient’s diet, and count individual amino acids from the whole protein sources (formula, food) and medical foods (special MMA/PA formulas). We then calculated the exact amino acid content of each diet. Our analysis showed that MMA patients prescribed medical foods take a lot more leucine than valine and isoleucine in their diets. Leucine is another amino acid that doesn’t feed into the MMA pathway, and therefore it was considered safe for MMA patients and it was included in high amounts in our MMA/PA medical foods. As a result, MMA patients on large amounts of medical foods (special MMA/PA formulas) end up receiving a large amount of leucine in their diets, which cause multiple effects at various levels in the whole body metabolism. This is reviewed in the papers and will be briefly discussed next.

Leucine is a branched chain amino acid essential to liver, muscle and fat tissue but, when given in excess, causes a depletion of the other branched chain amino acids, valine and isoleucine, because it causes them to be broken down more quickly. This happens because the dietary leucine (through its metabolite ketoisocaproic acid) is translated in our body as a signal of sufficient protein intake, so it results in the activation of the branched chain amino acid oxidation machinery, eventually resulting in low valine and isoleucine levels. Indeed, our study showed that higher intake of medical foods was strongly correlated with lower valine and isoleucine plasma amino acid levels. Moreover, the amino acid concentrations were directly affected by the timing of the blood draw – the closer to the medical food intake the lower the plasma valine and isoleucine values. Since both valine and isoleucine are essential, their deficiencies can cause problems with growth, bone health, and development. We showed that increased ratio of deficient over the natural protein correlated with poor growth outcomes (weight, height, muscle mass, bone density). This association cannot prove a cause-and-effect relationship between the amino acid deficiencies and the poor growth outcomes we observed because we only have information about the diet at one point in time. A large prospective clinical trial would be needed for that.

Our study provides significant insight to help better guide dietary management of MMA/PA patients. Understanding the effects of leucine on the plasma concentrations of valine and isoleucine will help physicians and dieticians interpret the plasma amino acid concentrations more accurately and adjust the diet prescriptions accordingly. If only valine and isoleucine are low, instead of supplementing the amino acids or increasing the whole protein, clinics need to appreciate this as a leucine

[ MEDICAL FOODS CONTINUED FROM PREVIOUS PAGE ]

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effect and lower the relative amount of medical foods/MMA/PA formula in the patient’s diet prescription. We presented an illustrative example in the paper, where, in collaboration with the treatment team from the University of Iowa, we were able to show that reducing the intake of medical foods resolved amino acid deficiencies without having to increase the protein intake in two patients with cblB deficiency.

Moreover, a higher than normal leucine plasma concentration can compete for the uptake of essential amino acids into the brain (valine, isoleucine, methionine and other) through an amino acid transporter called LAT1. This could be a double edged sword: we may want to block the valine and isoleucine uptake to the brain during a crisis, to lower the brain MMA production, but cannot deprive a young and growing brain of essential nutrients which could result in poor brain growth and possibly functional deficits.

These mechanisms are especially relevant for the second paper that focused on cblC deficiency. We strongly argue against the use of medical foods in patients with cblC, as these formulas were designed for patients with isolated MMA and PA. cblC patients have a low increases of methylmalonic acid , but their primary enzymatic defect affects their ability to synthesize the amino acid methionine from homocysteine, a reaction that depends on vitamin B12. As a result, management of cblC includes taking intramuscular vitamin B12 injections and betaine; supplements that help the body metabolize the amino acid homocysteine and increase methionine synthesis. Methionine is a very important amino acid for the brain. The medical foods designed for patients with isolated MMA contain no methionine and so when patients with cblC take

medical foods, they are restricting the exact amino acid that needs to be increased. In addition, the relatively high leucine content of medical foods may block methionine and other amino acid transport into the brain, where they are needed for brain growth. We describe our experience with 28 early onset cblC patients in this study, ranging in age from 2 to 27 years. A subset of nine participants received medical foods while another six followed protein-restricted diets. Both groups had lower growth rates, including decreased head circumference, than other patients who were on natural diets that provided the recommended daily allowance of

protein. Another case scenario was provided by the treatment team from Tulane University. It showed that increasing natural protein intake and discontinuing methionine-restricted medical foods helped improve head growth and blood amino acid concentrations in an infant with cblC.

Both of these studies highlight the lack of experimental and clinical trial data to support the current dietary management practices used to treat patients with varied forms of methylmalonic acidemia, and underscore the community need for more rigorous clinical studies of medical foods in the treatment of patients with IEMs.

Our studies emphasize the importance for patients and families with very rare disorders to participate and encourage research efforts for their respective conditions. It is the only way to collect information in an objective and systematic way, critically review our treatments and develop better therapies. WE WANT TO EXPRESS OUR GRATITUDE TO ALL THE PATIENTS, THEIR FAMILIES AND REFERRING PHYSICIANS FOR ALLOWING US TO PARTICIPATE IN THEIR CARE AND FOR THEIR SUPPORT OF OUR RESEARCH STUDIES. To the families, we again want to acknowledge that our partnership has been critical to understand MMA and cobalamin disorders, which we hope will lead to better therapies for all patients with organic acidemias. If any patient, family, care provider or researcher has questions regarding this article or our studies, we would be delighted to further discuss.

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EPI -743

(Vatiquinone) manufactured and provided by Edison Pharmaceuticals, Inc. and is one of the eight naturally occurring forms

of vitamin E. It is broadly classified as an antioxidant. EPI-743 has been

identified as a potent rescue agent in multiple primary patient fibroblast models of inherited

mitochondrial respiratory chain disease and diseases of metabolism. EPI-743 functions as a cofactor for the regeneration of Glutathione, an essential metabolite significantly depleted in patients with oxidative stress.

It is believed to use the same pathway as Vitamin E uses to be absorbed by being incorporated into dietary fats mixed with bile acids and salts. EPI-743 is a thick yellow oil administered orally or per g-tube as a mixture with Sesame oil at a concentration of 100 mg/mL, with meals. It crosses the blood-brain barrier and has been found in cardiac muscle.

It has been studied in Mitochondrial Electron Transport Chain defects, Metabolic and Mitochondrial Disorders, Visual and Neurologic effects in Cobalamin C, Leber’s Heritary Optic Neuropathy, Leigh Syndrome, Pearson Anemia, Friedreich’s Ataxia, Rett Syndrome

Protective Effects on Noise-induced Hearing Loss, Adults with Tourette Syndrome and Parkinson Disease. Most studies have been open label and results have been mixed in small numbers of patients.

The current NHGRI trial at NIH opened June 2012 and is a double-blind, placebo-controlled, cross-over design involving 20 children between 2-11 years of age with a 2 month washout period between treatment arms. “Standard of Care” mitochondrial supplements are not stopped or modified throughout the trial. In July of 2014 an Extension Arm was started for all patients who complete the 14-month trial without an adverse drug event while a rolling admission to complete the study is underway. We are not currently recruiting new patients and hope to complete this study in the next 2 years. However new studies may be in development to address other metabolic disorders, though nothing is definitely planned yet.

UPDATE:

Epi-743 LYNNE A. WOLFE, MS, CRNP, BC

NOVEMBER 2015

Give the Gift of Courage.

The “Be Brave” fundraiser bracelets for OAA are still available at www.bravelets.com/bravepage/organic-acidemia-metabolic-disorders

There are quite a few selections to choose from and remember OAA receives $10 for every sale.

BE BRAVE

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Jennifer Lynanne Mabbott was born November 10, 1996. As a baby, Jen was very quiet and content. She was somewhat of a reserved baby. When people would baby talk to her and try to get a smile out of her, she’d usually give them a blank look. But whenever it was time to leave she’d be sure to give everyone a kiss. A true test to Jen’s character, because all through her life she’s been quiet and shy, but as she gets to know you she opens up and shows you that she really cares.

Jen was quiet most of the time, but she heard every word spoken. She also had the memory of an elephant. Whether it was the date of an event, or something someone said, Jen had it on the top of her head. She was quick to call any of us on discrepancies in our stories or let us know when our facts didn’t match up. She was strong and determined. No matter how bad she felt in or out of hospital, if a new nurse or person came in and asked how she was doing, she would always reply “fine”. When she got to a set of stairs at school and one of the E.A.’s would offer her a hand, she would ALWAYS turn them down and say, “No I got it”. She never wanted anyone’s pity and wanted to show them that she could do it herself.

At only 7 months old she was diagnosed with a very rare metabolic disorder. Methyl Malonic Acidemia, or easier said MMA. In laymen’s terms, MMA means that Jen was missing the enzyme required to break down proteins. At age 4 she had a stroke, which gave her the mobility issues she had. The odd thing was that the stroke only affected

her mobility, not her memory. So she could remember that she could walk and talk, but she had to reteach herself how to do so. Even though her mobility skills didn’t fare so well in the long run, we can’t say the same about her speech… After speech therapy, there was no keeping her quiet. At age 11 Jen was diagnosed with beginning of renal failure. At 18 it was determined that Jen was in stage 5 renal failure. This meant that she would need to start dialysis. In May 2015 she was diagnosed with cardiomyopathy. So as you can see Jen had a lot of medical issues, but not many of us knew because she was never one to complain or look for pity.

The saying “It takes a village to raise a child” seems to ring true when thinking of everyone who played an instrumental role in Jen’s life.

Jen had a challenging and difficult life at times, but by no means did her disease define her. She did so much with her time here on earth and carved a place into all of our hearts. I read the posts on Jen’s Facebook and talked to a lot of people about Jen since she passed, and every single person has said that they’ve learnt so much from her. Shelley was once told that Jen was put on this earth to learn from, and I think we can all attest to that today. She is a true inspiration and we’re all better people for knowing her.

ANDREW MABBOTT, JENNIFER’S COUSIN AND GOD FATHER.

EXCERPTED FROM HER EULOGY.

I’M NOT THE TEENAGER YOU HAD IN MIND.

PEOPLE THINK I’M QUIET

BUT ONCE I GET TO KNOW YOU I DON’T STOP TALKING. PEOPLE THINK I’M LAZY

BUT I’M ALWAYS ON THE MOVE PEOPLE THINK I DON’T LISTEN

THE TRUTH IS I LISTEN TO WHAT PEOPLE TELL ME TO DO

MOST OF THE TIME PEOPLE THINK I’M A GOOD STUDENT

THE TRUTH IS I DON’T STUDY PEOPLE THINK I’M YOUNGER THAN I AM

I ’M 18 YEARS OLD I ’M NOT THE TEENAGER YOU HAD IN MIND PEOPLE THINK I WON’T BE ABLE TO GRADUATE

BUT I GRADUATE NEXT MONTH PEOPLE THINK I’M NOT SMART

BUT I GET GOOD GRADES IN SCHOOL I ’M NOT THE TEENAGER YOU HAD IN MIND

JENNIFER MABBOTT

Hi OAA family!

I tried writing something to put on this page, but I kept referring back to Andrew’s eulogy, so thought this was the best way to give an outline of Jennifer’s life. I miss her terribly, she was my partner, my best friend, my soul mate & my whole heart. But I know she is now pain free & disease free & still always by my side!

NOVEMBER 10, 1996 – SEPTEMBER 16, 2015

In Memory : Jennifer Lynanne Mabbott 18yrs MMA mut0

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Organic Acidemia Association (OAA) provides information and support to parents and professionals dealing with a set of inborn errors of metabolism collectively called organic acidemias. The OAA is a volunteer organization registered with the IRS as a 501(c)(3) non-profit corporation. Donations to the OAA are tax deductible. OAA publishes a newsletter 3 times a year, hosts a Google Group for information exchange and maintains a website. Services are funded by corporation & individual membership donations. Annual membership donation of $25 (US) and $35 (international) plus $5 for the family roster is requested, but not required. Our 501(c)(3) non-profit status qualifies OAA for United Way donations through their write-in option. If there is a write-in option, just write “Organic Acidemia Association” in the blank line on your pledge card. Donations can also be made at OAA’s website through the “PayPal” and the “Network for Good” option.

The information contained herein does not necessarily represent the opinions of our Board of Medical Advisors or Board of Directors Letters and photographs sent to OAA become the property of OAA and may be used or edited at the discretion of the OAA staff. Names or information will be kept confidential only if specifically requested in writing This newsletter does not provide medical advice. You should notify your health care provider before making treatment changes.

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ANNUAL DONATION CHANGE OF ADDRESS Please accept $_______________ as our annual tax deductible donation to the Organic Acidemia Association. Suggested membership donation is $25 (US) and $35 (international). Extra funds are welcome and can be designated for research, OAA operating expenses, or to help others attend conferences.

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