Ornithine Transcarbamylase Deficiency

Ornithine Transcarbamylase Deficiency Ornithine Transcarbamylase Deficiency:  An Inborn Error of Metabolism Marisa Houser The body’s metabolism is responsible for all the physical and chemical processes that convert or use energy. One of these processes is breaking down and digesting food. (National Institutes of Health , 2014) Food that is not broken down properly can lead to a buildup within the body and can be toxic or interfere with the body’s normal function. This build up can present with many different symptoms. Some of these symptoms can lead to developmental delays especially if left untreated or not controlled.(National Institutes of Health , 2013) The disorders that will not allow the body to properly turn food into energy are known as, inborn errors of metabolism. Though these are considered rare genetic disorders, there are many. Here, however, we will focus on just one, Ornithine Transcarbamylase Deficiency. Ornithine Transcarbamylase (OTC) deficiency is the most common urea cycle disorder affecting 1 in every 30,000 people. The urea cycle is the body’s way to dispose of excess nitrogen causing a buildup of ammonia within the body. 34% of patients will present within the first 30 days of life. (Sloas, 2013) These patients appear normal with no symptoms at birth but by day 2 to 3 they are extremely ill when they suffer from the first substantial buildup of ammonia in the body (˃150 µmol/L), also known as a hyperammonemic episode. (Jones, 2013) These patients may present with vomiting, poor feeding, irritability, fever and limpness. Prompt action needs to be taken to avoid critical long term affects. Some long term effects from hyperammonia can include seizures, swelling of the brain, developmental delays and liver failure. Many will not survive their first hyperammonemic episode and those that do will become hyperammonemic again. (Lichter-Konecki U, 2013) Late onset and partial disease of OTC deficiency disorder can also occur. Both late onset and partial disease are rare in both males and females. In either situation most will suffer a hyperammonemic episode at some point in their life. They may show mild presentation or not present at all until they suffer from severe illness, fasting, pregnancy or a new medication. These patients may present with anorexia, fever, irritability, rapid breathing, low muscle tone, vomiting, diarrhea/constipation, altered mental status, sleepiness, combativeness, psychosis, tremor, seizures and coma. (Sloas, 2013) All will also suffer from some type of neurological disorder such as developmental delays, learning disabilities, intellectual disabilities and attention deficit hyperactivity disorder (ADHD).(Lichter-Konecki U, 2013) When we eat, enzymes help break the food down so that our bodies can absorb the nutrients from the food. If the enzyme needed to break down the nutrients is nonexistent or deficient it halts one of the steps in the breakdown of our food for energy, and causes disease. When we eat protein it is broken down into essential and non-essential amino acids. The amino acids are converted to pyruvate then to oxaloacetic acid at which point they are introduced to the Krebs cycle. The Krebs cycle is where the majority of the energy from the food we eat is made. (ONeill, 2013) The Urea cycle is made up of five steps. The first step is the conversion of bicarbonate and ammonia to carbamyl phosphate. Next is the formation of citrulline from ornithine and carbamyl phosphate. The third step is the conversion of citrulline and aspartate to argininosuccinate. The fourth step is the cleavage of argininosuccinate to form arginine. The final step is the degradation of arginine to form urea and ornithine. (Figure 1) At this point the urea can be disposed of through the body in urine. This process is catalyzed by the enzymes that exist in the liver. One of these enzymes is Ornithine Transcarbamylase. (Shambaugh III, 1977) Ornithine Transcarbamylase is an enzyme of the liver and intestinal mucosa that catalyzes the breakdown of citrulline from ornithine and carbamyl-phosphate. In OTC deficiency this process is halted. Now the body cannot detoxify ammonia to make urea, a substance that is disposed of through urination and the ammonia builds up within the system. (Herin glake, Boker, Manns, 1997) The 3rd step, the conversion of citrulline and aspartate to argininosuccinate, is the link between the Krebs cycle and the Urea cycle. Figure 1. Urea Biosynthesis (Shambaugh III, 1977) Figure 2 Urea Cycle â€Å"The urea cycle functions primarily in the liver, and is a metabolic pathway that detoxifies ammonia by converting it into urea. Ammonia is generated from the conversion of proteins and nucleic acids in our diet as well as due to normal cellular turnover. Defects of the urea cycle result in hyperammonemia which can progress to brain edema and result in cognitive impairment or death.† (Childrens National Medical Center, 2007) OTC deficiency is a disorder involving the mutation of the ornithine transcarbamylase gene, located on the short arm of the X chromosome at position 21.1. (Sloas, 2013) (Figure 3) OTC deficiency is an X linked disorder and therefore will mostly affect males, especially early onset as a baby. More than 300 mutations have been identified in patients that have OTC deficiency. Most are single base alterations that alter the amino acid code. Most families have mutations that only occur within their own genome usually found at the CpG dinucleotides. CpG dinucleotides are where the cytosine nucleotide and guanine nucleotide are next to each other on the DNA. According to the Children’s National Medical Center, these are â€Å"mutation hotspots†. (Childrens National Medical Center, 2007) Figure 3. Cytogenetic Location: Xp21.1. Molecular Location on the X chromosome: base pairs 38,352,482 to 38,421,449 (U.S National Library of Medicine, 2015) There are no measures that prevent OTC deficiency all together, however there are preventative measures that can be used to help reduce or avoid hyperammonemic episodes. Families can provide doctors with their family health history and undergo genetic testing to help the family make informed medical and personal decisions. If either parent is a carrier, testing can be done to diagnose OTC deficiency prenatally. This can help the healthcare team avoid the initial and often critical first hyperammonemic episode. For patients that are not diagnosed prenatally but within the first few days of life, reducing the concentration of ammonia in their system rapidly is critical. This can be done by hemodialysis. Hemodialysis is a process used to clean your blood by pumping it through a special machine. The faster the ammonia level is lowered the greater the chance of avoiding severe brain damage from the buildup of ammonia in the bloodstream. In addition protein intake should be restricted, especially animal proteins as these are high in nitrogen and lead to hyperammonemic episodes. Many partial and late onset OTC deficiency patients practice a vegetarian diet to avoid the risk of elevated ammonia levels. Another course of treatment is finding an alternate pathway for nitrogen excretion. (Lichter-Konecki U, 2013) Phenylbutyrate and oral sodium benzoate are nitrogen scavengers. They provide an alternate way for the body to dispose of nitrogen and safely take in more protein. Liver transplants are a common course of treatment as well. The transplant can prevent reoccurring hyperammonemic episodes and long term neurological effects. These are typically performed by age sixth months. Those diagnosed with partial OTC deficiency or late onset may also be liver transplant candidates if they suffer from frequent hyperammonemic episodes. (Lichter-Konecki U, 2013) Researchers are investigating some new therapies to manage OTC deficiency. Hypothermia for neuroprotection, cooling to body down has been shown to reduce ammonia production by lowering the body’s metabolism overall. Liver cell transplant is being studied to see if I can temporarily stabilize critically patients while they are waiting for a liver transplant. Human induced pluripotent stem (iPS) cells are being considered. This therapy would use the patient’s cells to generate stem cells that can then be induced to become liver cells. Gene therapy could possibly be used to correct the disorder in the new cells and then used to for liver regeneration in the patient. (Lichter-Konecki U, 2013) These promising new approaches continue to give hope to patients and their families. Works Cited Childrens National Medical Center. (2007). Welcome to the Ornithine Transcarbamylase website . Retrieved from Ornithine Transcarbamylase Deficiency Website: http://ureacycle.cnmcresearch.org/otc/ Heringlake, S., Boker, K., Manns, M. (1997). Fatal clinical course of ornithine transcarbamylase deficiency in an adult heterozygous female patient. Digestion 58.1, 83-6. Jones, P. M. (2013). Altered Mental State in a Teenager. Clinical Chemistry 59.10, 1442-4. Lichter-Konecki U, C. L. (2013, August 29). Ornithine Transcarbamylase Deficiency. Retrieved from GeneReviews: http://www.ncbi.nlm.nih.gov/books/NBK154378/ National Institutes of Health . (2013, June 9). Inborn errors of metabolism. Retrieved from MedLine Plus: http://www.nlm.nih.gov/medlineplus/ency/article/002438.htm National Institutes of Health . (2014, August 7). Metabolism . Retrieved from MedLine Plus: http://www.nlm.nih.gov/medlineplus/ency/article/002257.htm ONeill, M. (2013, January 4). Metabolic Pathways of Proteins, Carbohydrates and Fats in Humans. Retrieved from Ketopia wonderful low card science: http://ketopia.com/metabolic-pathways/ Shambaugh III, G. E. (1977). Urea biosynthesis I.The urea cycle and relationships to the citric acid cycle. The American Journal of Clinical Nutrition, 2083-87. Sloas, H. A. (2013). At the intersection of toxicology, psychiatry, and genetics: a diagnosis of ornithine transcarbamylase deficiency. The American Journal of Emergency Medicine 31.9, 1420.e5.

Essay --

Upon the invasion of foreign powers, the central government secured its authority over China and integrated nationalism into its domestic and foreign policies in order to restore stability, and repel against foreign influences. China, before nineteenth century, existed as a heterogeneous Empire, unified by the 5000 year old â€Å"Great Civilization†; however, upon foreign invasion in nineteenth century, China was forced to re-evaluate their position on the international level. Modern Chinese nationalism is derived from traumas inflicted by European and Japanese imperialists and colonists (Melancon 856-874; Chung 5). The concept of Century of National Humiliation was created in order to commemorate the historic traumas and protect the nation’s sovereignty from foreign powers. Over time, Chinese society has come to embrace their glorious civilization and accepted their weaknesses which had caused them to be victimized in the past. Now, the central government uses strict principles to assure China’s moral position on foreign policies. For example, on April 1st, 2001, there was a mid-air c...

Importance of Literature Essay

Literature is the foundation of life. It places an emphasis on many topics from human tragedies to tales of the ever-popular search for love. While it is physically written in words, these words come alive in the imagination of the mind, and its ability to comprehend the complexity or simplicity of the text. Literature enables people to see through the lenses of others, and sometimes even inanimate objects; therefore, it becomes a looking glass into the world as others view it. It is a journey that is inscribed in pages, and powered by the imagination of the reader. Ultimately, literature has provided a gateway to teach the reader about life experiences from even the saddest stories to the most joyful ones that will touch their hearts. From a very young age, many are exposed to literature in the most stripped down form: picture books and simple texts that are mainly for the sole purpose of teaching the alphabet etc. Although these are not nearly as complex as an 800-page sci-fi novel, it is the first step that many take towards the literary world. Progressively, as people grow older, they explore other genres of books, ones that propel them towards curiosity of the subject, and the overall book. Reading and being given the keys to the literature world prepares individuals from an early age to discover the true importance of literature: being able to comprehend and understand situations from many perspectives. Physically speaking, it is impossible to be someone else. It is impossible to switch bodies with another human being, and it is impossible to completely understand the complexity of their world. Literature, as an alternative, is the closest thing the world has to being able to understand another person whole-heartedly. For stance, a novel about a treacherous war, written in the perspective of a soldier, allows the reader to envision their memories, their pain, and their emotions without actually being that person. Consequently, literature can act as a time machine, enabling individuals to go into a specific time period of the story, into the mind and soul of the protagonist. With the ability to see the world with a pair of fresh eyes, it triggers the reader to reflect upon their own lives. Reading a material that is relatable to the reader may teach them morals and encourage them to practice good judgement. This can be proven through public school systems, where the books that are emphasized the most tend to have a moral-teaching purpose behind the story. An example would be William Shakespeare’s stories, where each one is meant to be reflective of human nature – both the good and bad. Consequently, this can promote better judgement of situations, so the reader does not find themselves in the same circumstances as perhaps those in the fiction world. Henceforth, literature is proven to not only be reflective of life, but it can also be used as a guide for the reader to follow and practice good judgement from. The world today is ever-changing. Never before has life been so chaotic and challenging for all. Life before literature was practical and predictable, but in present day, literature has expanded into countless libraries and into the minds of many as the gateway for comprehension and curiosity of the human mind and the world around them. Literature is of great importance and is studied upon as it provides the ability to connect human relationships, and define what is right and what is wrong. Therefore, words are alive more than ever before.

The Criminal Justice System Is Complex - 1201 Words

Overview: The criminal justice system is complex and in need of several types of reforms, this is especially true in the juvenile justice system. In 2012, there were 1,319,700 arrests of juveniles in the United States (OJJDP) and this includes both violent and non-violent offenses committed by those under the age of 18. Policy reforms can offer alternatives to the incarceration of young offenders, by providing mental health, or addiction rehabs for those that are in need of it rather than locking them up. This not only helps keep the amount of juveniles down but also can be a preventative in recidivism. Some believe that juveniles should be punished by the same laws that apply to the adult offenders while others look to rehabilitation†¦show more content†¦Another factor for reform is that some policies â€Å"fail to calculate the long-term social costs of categorical punishment† (Scott Grisso, 1997 p. 139) when their behavior is affected by drug or alcohol addiction, family and/or behavioral issues that leads them to do criminal acts. Competing Interpretations: In a perfect world both conservatives and liberals would agree on everything, when it comes to policy issues and reforms that is not always the case. It is important that both sides come to an agreement on policy issues especially when it comes to the futures of young people as the decisions they make can either help or hinder those in the system. On the topic of criminal justice reform however, both sides seem to agree that reform is needed. 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