分类存档: 新闻 & 公告

基督教中号.

基督教中号. – 更新Febrary 2019

基督教中号.

基督教中号.

基督教, 也称为CJ, 是一个爱玩的五岁. 他喜欢听音乐, 舞蹈, 唱. 他最喜欢的活动包括与他的妹妹玩耍，观看YouTube视频. 基督教是在全天幼儿园和喜欢与他的朋友交往. 基督教在学校参加瑜伽俱乐部，他在体操参加, 网球, 魔术类, 和骑马穿过公园区. 他喜欢旅行，他的最爱逛的地方是大烟山.

基督教的姐姐是通过新生儿初筛诊断为丙酸血症, 因此，我们已经把危机管理计划的地方为他生. 中 48 他出生的时间, 我们接受了他的PA的诊断. Currently, 基督教吃 11 克蛋白质, 饮料Propimex-2, 并每天服用维生素. 我们似乎总是在流感季节在医院结束了, 但比其他的基督徒一直是非常幸福和健康的小男孩会议所有他的里程碑.

过去的故事 – 基督教 – age 3

基督教

基督教中号.

基督教, 也称为CJ, 是一个三岁跳舞机. 他喜欢听音乐，并有舞会在我们的厨房和地下室. 他是党的生命，始终使人们微笑. CJ参加学前教育一周两次，也参与足球和体操. 在家, 他喜欢跟着他的姐姐身边，努力发挥什么她是打. 他的超级英雄的玩具往往是对抗芭比娃娃. 像大多数其他三岁孩子, CJ爱汽车, 卡车, 他最喜欢的电视节目是爪子巡逻.

 

玛雅中号.

玛雅中号. – 二月更新 2019

玛雅中号.

玛雅中号.

玛雅是一个九岁的心上人. 她喜欢观看YouTube视频，并制作自己的影片为她MayaTV通道. 玛雅爱使煤泥，听她的iPod音乐. 她还喜欢旅行，与她的家人去度假. 玛雅是三年级和爱读书, 写草书, 和解决问题的乘法. 她加入了她的服务学习俱乐部在学校和体操参加, 魔术类, 网球, 戏剧, 和骑马穿过公园区.

玛雅从医院回家后确诊为丙酸血症. 我们很幸运，有通过新生儿初筛的快速诊断和避免任何代谢危机. 玛雅消耗 13 克蛋白质口服每天. 她喝Propimex-2，并采取多种维生素. 总体, 玛雅是一个快乐，健康的小女孩谁使每个人都笑着跟她的性格幽默.

玛雅 – 7 years old

玛雅中号.

玛雅中号.

玛雅是一个7岁, 有活力, 和热闹的小女孩. 目前，她是一年级，其中她最喜欢的科目是电脑课和体育课. 玛雅热爱旅行. 她最喜欢的旅游地点是任何涉及一个海滩和阳光. 她在整个夏天基本花费在她的祖父母的瑜珈熊露营地. 她喜欢“驾驶高尔夫球车”, swimming, fishing, 并试图捕捉青蛙. 玛雅喜欢尝试所有活动. 她曾参与过芭蕾, 嘻哈和水龙头类. 她一直在乐高俱乐部, 疯狂科学家俱乐部, 烹饪俱乐部, 艺术俱乐部. 她还一直试图体操和戏剧. 玛雅的喜爱爱好包括制作自己的视频，并与她所有的娃娃玩具玩.

玛雅是通过她的新生儿初筛确诊为丙酸血症. 随着早期检测, 我们能够避免任何重大危机. 目前玛雅消耗 13 克蛋白质口服和饮料Propimex-2每天. 她是不是所有她的医生的约会的忠实粉丝, 但她明白需要他们保持健康.

 

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?

丙酸血症 (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. 但, 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, 眼, 心, 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

https://clinicaltrials.gov/ct2/show/record/NCT02890342?term=propionic&rank=4

Contact information

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

[email protected]

or

NIH Clinical Center Patient Recruitment and Public Liaison Office

1-800-411-1222

 

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.

斯嘉丽Since 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 通讯

Reuben

Reuben

Reuben

Article from Spring 2013 通讯

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.

鲁本更新!

右王牌-手写在 1992 我当时正在上的创意写作课

鲁本将会 40 在他的下一个生日，所以可能是时候更新了. 自三月份以来他一直非常健康 2020. 鲁本参加我们教堂每周四天的日间活动和半天的活动, 一个星期一次.

他热爱棒球和 NFL 橄榄球的一切. 在许多个圣诞节和生日期间，他几乎收集了所有球队的球衣和帽子. 我们知道他对某事感到不安, 这很少发生, 当他扔下帽子时. 鲁本在一支特殊需要的棒球队和篮球队打球，他喜欢各种形式的蓝草音乐.

和鲁本住在一起就是早上受到 "祝福你妈妈". 他的笑声可以出于任何原因或根本没有原因，并且像普通感冒一样具有传染性. 他喜欢去教堂和去餐馆, 即使他可能不会吃任何东西, 他只是喜欢和人们在一起. 鲁本被任命为他姐妹的早期干预公司的幸福协调员，这也是她选择与有特殊需要的儿童一起工作的主要原因.

他所有的营养都是通过管饲的, Duocal 的混合物, Anamix 和 Ensure 会吃薯片或奇多.

他教会了我很多关于耐心、享受生活中的小事以及对任何事情感到满意的知识

来了.

如果您想谈论我们的孩子，请随时与我联系. 可以联系我：

Patt@CarolinaBehaviorand Beyond.com

Reuben

Propionic Acidemia Genetics Part 1

PA遗传学, 部分 1

 

丙酸血症 (PA) 是一个条件引起的基因，使丙酰基 - 辅酶A的变化 (辅酶A) 羧化酶. 基因 制成的 DNA 这是我们的遗传物质. 基因告诉我们的身体如何成长和功能的说明. 每个基因提供了在体内的各种生物过程的具体说明.

 

使该丙酰辅酶A羧化酶的基因被称为PCCA和PCCB. 这种酶有助于食物分解某些蛋白质和脂肪，使成化学能和其他产品的机体需要. 当在该基因的变化称为 突变, 的基因不能执行其正常功能. 如果这些基因不工作，身体无法分解脂肪和蛋白质, 有有机酸在体内积累可导致与PA相关的症状，例如呕吐, 弱肌张力, 发育迟缓.

 

如果有人有突变, 这是他或她出生时. 这些突变随机发生并且它们不被什么东西的人确实引起. 我们有各基因的两个拷贝. 我们继承了一份来自于父母. 如果某人有一个基因突变和一个基因可以正常工作, 它们被称为一 支架. 因为有一个工作基因拷贝意味着身体仍然能够分解脂肪和蛋白质运营商没有丙酸血症症状.

 

如果父母双方都丙酸血症携带者, 有一个 1 在 4 or 25% 具有丙酸血症的孩子机会. 这就是所谓的 常染色体隐性遗传 遗产. 该情况可能会影响男性和女性，一个人有继承2突变基因与PA的影响. 因此, 为了通过PA影响, 孩子有继承父母双方的基因突变. 如果一个孩子继承了一个工作基因和一个突变基因, 他们也将是一个载体

PA不会有症状. 如果一个孩子继承了两个正常拷贝

基因, 他们将不会是一个载体和不具备的条件.

 

 

要了解，如果你是PA的载体, 你可以有 基因检测. 我们的DNA是写在四个字母的代码. 基因检测的工作原理是通过读码就像一个拼写检查面色一变, 也被称为突变.

 

罗宾Hylind

遗传咨询的学生

西北大学

研究生课程遗传咨询

Gwen

 

Gwen M. – updated May 2015
My beautiful girl just turned 9 今年几岁了，简直就是奇迹. At 2 days of age, Gwen became catastrophically ill, her body temperature dropped below 90 度, 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, & 朋友. 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!!!!

迪伦Ĵ

迪伦Ĵ | 丙酸血症 | Age 2 1/2

迪伦结果表明：J出生在10月 12日, 2013 在沃科尼亚, 明尼苏达, 在称重 8 英镑, 2 ounces. 后迪伦诞生, 医生发现他有一个低于平均体温, 所以他们把他带回幼儿园温暖他，. 他被带回美国, 并从那里出来两天, 我们经历了一个正常, 健康的小男孩, 或者我们是这么认为.

在十月的清晨 15日, 只要 15 因为我们时间已经出院作为一个家庭的 3, 迪伦在演戏那样的陌生. 他很困, 似乎寒冷的触感. 我的老公, 亚当, 我把他的温度，他是在 95 度. 明知是不正常的, 我叫我的妹妹- 在- 法, 谁是NICU护士在这里的城市, 她告诉我们要尝试做皮肤上的皮肤温暖他，, 如果没有工作, 到大概拨打值班儿科医生. 但令我们失望, 一个小时过去了，他没有回暖所有, 即使一切后，我们曾尝试. 我叫值班的儿科医生，他告诉我们，看他在接下来的几个小时, 如果他仍然寒冷，还是很昏昏欲睡，不想吃, 我们可以等到把他带到儿科医生办公室那天早上在上午8点开, 或者我们可以带他到急诊室. 约一小时后, 我的丈夫拿起迪伦高达带到我这里来尝试和饲料, 而他的手臂无力地跌他的身体背后. 这是烙在我的脑海里的图像. 我们知道在那一刻，什么是错, 所以我们收拾他，在他的汽车座椅和开车把他送到急诊室. 一旦出现, 他们打量了他一下, 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, 但他们认为，他需要在明尼阿波利斯市中心被转移到一家儿童医院, 把他上呼吸机, 因为他正从工作，所以难以呼吸过于疲惫. 他离开房间, 我失去了它, 呼吸机, 我的小宝贝? 什么问题? 后来，医生回来说, 他居然相信他们也许可以只是尝试氧气, 所以他们在楼上他转移, 他们的新生儿重症监护病房, 看看我们可以得到它的控制之下.

就在那时, 该等待比赛开始. 他们做了多次验血, 在一个点来得出结论，他只是脱水. 他的血糖非常低, 而且他们认为他只是没吃饱. 时间过去了, 我们都在等待这并围绕多个郊区医院巡视的新生儿, 到达并期待在迪伦. 大约午饭时间, 医生走了进来，看着他，并告诉我们他认为迪伦仍然需要被转移到儿童医院的呼吸机被投入，因为氧气本身没有削减它. 当他告诉我们这, 一名护士走进来, 递给他一张纸, 到他看着, 回答说：“噢，我的天哪”, 离开房间. 我们被吓坏了, 但没想到的太多了吧. 几分钟后，他回来了，并告诉我们，迪伦的氨水平 900. 他看着我们很迷茫的脸，并告诉我们，这是非常, 很严重, 该正常范围是 10-35, 而迪伦可能不能使它. 我记得麻木, 的想法，我的品牌新的婴儿可能会死, 当一个小时前，我们刚刚还以为他是脱水. 医生离开了设立救护车把迪伦, 还没到儿童医院了, 但是到了明尼苏达大学儿童医院, 因为他需要特殊处理, 只适用于大学. 他需要放在透析.

我在迪伦救护车骑, 而这些都是最长 45 我的生活分钟. 我记得当时我想他会在救护车死, ，有什么我可以做, 我只是在前排座位坐起来祈祷. 当我们赶到医院, 它像一个场景动画的, 所有这些医生一拥而上我们, 告诉我，他们会一直在等待, 解释是怎么回事, 需要我签同意书，开始透析. 告诉我，在做透析 3 天大的婴儿是非常危险的, 但什么其他选择，确实我们有? 当我们来到他的氨已攀升至医院 1200. My husband and I, 和我们的家庭, 被领进我们等着听迪伦上的字家庭候车室. 就在这个时候，我们被介绍给我们的代谢医生. 她来了，遇见了我们，并描述了她相信Dylan有. 一种罕见的遗传疾病, 在那里，他不能正确分解蛋白质, 而不是将它分解, 他只会分解到某一个点，然后坏事 (丙酸和氨), 将备份在他的系统. 同在一处高，因为它是, 它被毒害他的器官. 他们告诉我们，他们认为他的大脑肿胀，什么脑损伤他从高氨氮收到他们不能肯定, 他们将采取超声波和核磁共振检查, 这两者出来相当不错的, 但真正的时间会告诉.

许多小时后, 透析开始, 和一名护士进来, 并且说的话, 我永远不会忘记“我知道这一直是你生命中最糟糕的一天, 但我想给你一些好消息, 迪伦的氨是90“! 一样快，他生病了, 他得到了更好的一样快. 他们能够赶迪伦的新生儿筛查结果和证实了他丙酸血症诊断. 医生现在有一个诊断，并能对他进行治疗. 随着日子一天天的过去了ICU, 他氨稳定, 他们能够开始他Propimex和母乳的低蛋白饮食, 他居然真的很好. 我们能够刚过回家 7 在ICU天.

生活之后迪伦似乎去非常好, 和对我们是“正常”的. 他是一个很好吃, 总是吃蛋白，他需要在一天获得热量的量和被正常显影. 我每天会检查他酮在他的尿 (我们的医生认为我是检查与其说是一个有点疯狂, 但它是我的指标是事关), 而且他们总是消极的，直到他正要 5 months old. 迪伦几乎每天开始获取跟踪小酮在他的尿. 我们将努力推动更多的流体, 但他们仍然会涨回去. 他正在吃他所有的瓶子非常好动，演戏完全正常. 但, 一旦我们看到酮, 我们将带来他在急诊室，他的氨会很高, 在100的. 最可怕的是, 他从来没有演过不同, 从未表现出他的招牌氨高, 除了酮.

在二月至五月间的暂时进出医院周后, 我们的代谢医生决定开始他Carbaglu, 以帮助保持他的氨检查. 当我们从医院在四月下旬开始Carbaglu后出院, 我们遇到了与我们的代谢医生跟进预约. 正是在这个约会迪伦的医生坐在我们失望，并告诉我们，她认为迪伦需要肝脏移植. 你看, 他们从来没有能够告诉我们某些如果Dylan有PA与否的一个更严重的情况下，, 因为基因检测已完成后，, 它回来了，无论他的突变从未见过. 所以，我们种不得不等待，看看他怎么做. 我们被震惊了, 从未有过，我们认为肝移植手术会是这样，我们将讨论对迪伦. 我和我丈夫回家了几个星期想过这个问题, 祈祷吧, 哭一下吧, 它研究, 其他家长有故事，已通过了这, 并最终决定，我们不想等到另一场危机发生的迪伦和他有脑损伤或更糟, 我们希望迪伦保持迪伦. 所以在五月 8日 今年, 当迪伦 7 months old, 我们放置在移植名单迪伦获得一个新的肝脏.

On July 24日, 我们得到了他们有一个新的肝脏迪伦通话. 我们丢弃我们在做什么，并跑到了医院，他们做了所有的手术前的准备工作, 我们准备, 又等了字何时机关将在明尼苏达州和手术时将开始. On July 26日, 手术发生. 我丈夫和我走迪伦到运前的房间，把他交给移植小组. 我们被引导到我们与家人等待着家庭候车室 8 时间很长. 当外科医生走了出来, 在他的脸上露出了笑容, 并告诉我们，它已经非常顺利, 它是这样一种解脱. 我们被带到了我们能够看到迪伦PICU, 和害怕，因为我是看他, 当我们做, 他看起来那么好. Yes, 他迷上了这么多管和线, 他被肿, 但他看起来就像我们的孩子. 我们住在医院 18 天视迪伦恢复. 他的身体接受了新的肝脏非常好, 和我们生命中最美好的时刻之一, 是当我们的新陈代谢医生进来告诉我们，他们对迪伦采取手术已经显示后有机酸测试，他在他的身体没有任何丙酸! 这真是一个奇迹.

这是近 2 因为迪伦年有他的移植，他是做奇妙. 他曾因为并发症少，但他通过他们得到出色. 迪伦将在抗排斥药物，他的一生. 有说他可能进入拒绝在任何时候恐惧, 但如果发现及时, 这是非常可治疗. 在这里，在明尼苏达州, 与我们的医生, 他们将保持非常密切关注他. 我们还没有关于如果肝脏会持续一生大量的研究, 或者，如果他需要一个新的最终, 但在同一时间, 我们没有对什么PA确实给体长期一吨的数据. 我们的代谢医生正在非常谨慎与他, 他们让他在他的代谢公式只是直到去年10月，我们想看看他有什么实验室做了，如果他走了它，到目前为止，他一直保持稳定. 他仍然在限制蛋白饮食, 现在他得到30-35克，每天. 因为移植在他的变化一直十倍. 之前，他曾语气低沉而现在他的语气是如此美好, 他运行，并爬上就像所有其他 2 ½当我们打岁在公园! 虽然这是最艰难的决定，我的丈夫和我都做过, 这是一个正确的决定对我们, 我们希望迪伦带领他可以最好的生活, 而且，即使有这么多风险, 我们不知道 100% 什么样的未来将举行, 这是值得的, 因为他是如此开心，也很健康 2 ½岁的小男孩!

博士. 宫崎

博士. 彻宫崎, M.D.,Ph.D.

The University of Texas Southwestern Medical Center Dallas, 得克萨斯州

Prior to becoming a 501(Ç)3, the PAF established a Propionic Acidemia Fund at UT Southwestern Medical Center in Dallas, Texas to promote the studies of Dr. 彻宫崎. With PAF’s help, this fund raised over $90,000. 博士. 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. 博士. 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.

博士. 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.

博士. Barry August 2006 Progress Update

Michael A. Barry

八月 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. 肖恩Hofherr, a graduate student in Dr. Barry’s laboratory is pursuing this project for his Ph.D. thesis. 到目前为止，, 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, 博士. 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. 例如, 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. 例如, one might predict that the liver expresses the highest level of PCCA given its role in metabolizing excess amino acids and fatty acids. 反过来, 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. 鉴于这些问题，, 博士. 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. 但, 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.