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Columnmate Beta Thal Hba2 Control-abnormal

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Last Updated: 20 November 2020

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Beta thalassemia is a blood disorder that reduces production of hemoglobin. Hemoglobin is an iron-containing protein in red blood cells that carries oxygen to cells throughout the body. In people with beta thalassemia, low levels of hemoglobin lead to lack of oxygen in many parts of the body. Affected individuals also have shortage of red blood cells, which can cause pale skin, weakness, fatigue, and more serious complications. People with beta thalassemia are at increased risk of developing abnormal blood clots. Beta thalassemia is classified into two types depending on severity of symptoms: thalassemia major and thalassemia intermedia. Of the two types, thalassemia major is more severe. Signs and symptoms of thalassemia major appear within the first 2 years of life. Children develop life-threatening anemia. They do not gain weight and grow at the expected rate and may develop yellowing of skin and whites of eyes. Affected individuals may have enlarge spleen, liver, and heart, and their bones may be misshapen. Some adolescents with thalassemia major experience delay puberty. Many people with thalassemia major have such severe symptoms that they need frequent blood transfusions to replenish their red blood cell supply. Over time, influx of iron-containing hemoglobin from chronic blood transfusions can lead to buildup of iron in the body, resulting in liver, heart, and hormone problems. Thalassemia intermedia is milder than thalassemia major. Signs and symptoms of thalassemia intermedia appear in early childhood or later in life. Affected individuals have mild to moderate anemia and may also have slow growth and bone abnormalities. Mutations in HBB gene cause beta thalassemia. The HBB gene provides instructions for making protein called beta-globin. Beta-globin is a component of hemoglobin. Hemoglobin consists of four protein subunits, typically two subunits of beta-globin and two subunits of another protein called alpha-globin. Some mutations in HBB gene prevent production of any beta-globin. Absence of beta-globin is referred to as beta-zero thalassemia. Other HBB gene mutations allow some beta-globin to be produced but in reduced amounts. A reduced amount of beta-globin is called beta-plus thalassemia. Having either I 0 or I + thalassemia does not necessarily predict disease severity, However; people with both types have been diagnosed with thalassemia major and thalassemia intermedia. Lack of beta-globin leads to a reduced amount of functional hemoglobin. Without sufficient hemoglobin, red blood cells do not develop normally, causing a shortage of mature red blood cells. A low number of mature red blood cells leads to anemia and other associated health problems in people with beta thalassemia. Thalassemia major and thalassemia intermedia are inherited in autosomal recessive pattern, which means both copies of the HBB gene in each cell have mutations. Parents of individuals with autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition. Sometimes, however, people with only one HBB gene mutation in each cell develop mild anemia.

* Please keep in mind that all text is machine-generated, we do not bear any responsibility, and you should always get advice from professionals before taking any actions.

* Please keep in mind that all text is machine-generated, we do not bear any responsibility, and you should always get advice from professionals before taking any actions

Introduction

Thalassaemia is the name for a group of inherited conditions that affect substance in the blood called haemoglobin. People with thalassaemia produce either no or too little haemoglobin, which is used by red blood cells to carry oxygen around the body. This can make them very anaemic. It mainly affects people of Mediterranean, South Asian, southeast Asian and Middle Eastern origin. There are different types of thalassaemia, which can be divided into alpha and BETA thalassaemias. BETA thalassaemia MAJOR is the most severe type. Other types include BETA thalassaemia INTERMEDIA, alpha thalassaemia MAJOR and haemoglobin H Disease. It's also possible to be carrier of thalassaemia, also know as having thalassaemia trait. Being a BETA thalassaemia carrier will not generally cause you any health problems, but you're at risk of having children with thalassaemia.


Causes of thalassaemia

Most beta thalassemia cases are caused by mutation in the HBB gene. In extremely rare cases, loss of genetic material that includes HBB gene causes disorder. Genes provide instructions for creating proteins that play a critical role in many body functions. When gene mutation occur, protein product may be faulty, inefficient, or absent. Depending upon the functions of a particular protein, this can affect many organ systems of the body. Individuals with beta thalassemia minor have mutation in one HBB gene and are carriers for disorder. Individuals with beta thalassemia intermedia or major have mutations in both HBB genes. Normal hemoglobin is made up of specialized proteins called globins, specifically two alpha chains and two beta chain proteins attach to the central heme ring. The HBB gene creates beta globin protein chains. Mutation in one HBB gene results in either reducing or no production of beta chains from that gene. Regardless, second copy of the HBB gene functions normally and produces enough beta chain protein to avoid symptoms, although red blood cells are still abnormally small and mild anemia can still develop. Mutation in two HBB genes results in either significantly reduced levels of beta chains or almost complete lack of beta chains. Reduction or lack of beta globin protein chains leads to imbalance with normally-produce alpha globin protein chains and, ultimately, defective formation of red blood cells, lack of functional hemoglobin, and failure to deliver sufficient amounts of oxygen to the body. In individuals with dominant beta thalassemia, mutated HBB gene creates an extremely unstable type of hemoglobin. Affected individuals have ineffective red blood cell formation. Researchers believe that additional factors influence severity of beta thalassemia major and intermedia including modifier genes. Modifier genes, unlike genes that cause beta thalassemia, affect clinical severity of the disorder. More research is necessary to discover various modifier genes associated with beta thalassemia and their role in the development of the disorder. Beta thalassemia is inherited in autosomal recessive pattern. Recessive genetic disorders occur when an individual inherits abnormal genes from each parent. If an individual receives one normal gene and one abnormal gene for disease, person will be carrier of disease, but usually will not show symptoms. The risk for two carrier parents to both passing abnormal genes and, therefore, having affected child is 25 % with each pregnancy. The risk of having a child who is a carrier, like parents, is 50 % with each pregnancy. The chance for a child to receive normal genes from both parents is 25 %. The risk is the same for males and females.

* Please keep in mind that all text is machine-generated, we do not bear any responsibility, and you should always get advice from professionals before taking any actions.

* Please keep in mind that all text is machine-generated, we do not bear any responsibility, and you should always get advice from professionals before taking any actions

Etiology

Alpha Thalassemia is a blood disorder that reduces production of hemoglobin. Hemoglobin is a protein in red blood cells that carries oxygen to cells throughout the body. In people with characteristic features of alpha Thalassemia, reduction in the amount of hemoglobin prevents enough oxygen from reaching the body's tissues. Affected individuals also have shortage of red blood cells, which can cause pale skin, weakness, fatigue, and more serious complications. Two types of alpha Thalassemia can cause health problems. The more severe type is known as hemoglobin Bart hydrops fetalis syndrome, which is also called Hb Bart syndrome or alpha Thalassemia major. The milder form is called HbH disease. Hb Bart syndrome is characterized by hydrops fetalis, condition in which excess fluid builds up in the body before birth. Additional signs and symptoms can include severe anemia, enlarge liver and spleen, heart defects, and abnormalities of the urinary system or genitalia. As result of these serious health problems, most babies with this condition are stillborn or die soon after birth. Hb Bart syndrome can also cause serious complications for women during pregnancy, including dangerously high blood pressure with swelling, premature delivery, and abnormal bleeding. The HbH disease causes mild to moderate anemia, hepatosplenomegaly, and yellowing of eyes and skin. Some affected individuals also have bone changes such as overgrowth of the upper jaw and an unusually prominent forehead. Features of HbH disease usually appear in early childhood, and affected individuals typically live into adulthood. Alpha Thalassemia typically results from deletions involving HBA1 and HBA2 genes. Both of these genes provide instructions for making a protein called alpha-globin, which is a component of hemoglobin. People have two copies of HBA1 Gene and two copies of HBA2 Gene in each cell. Each copy is called an allele. For each Gene, one allele is inherited from the person's father, and the other is inherited from the person's mother. As a result, there are four alleles that produce alpha-globin. Different types of alpha Thalassemia result from loss of some or all of these alleles. Hb Bart syndrome, most severe form of alpha Thalassemia, results from loss of all four alpha-globin alleles. HbH disease is caused by loss of three of four alpha-globin alleles. In these two conditions, shortage of alpha-globin prevents cells from making normal hemoglobin. Instead, cells produce abnormal forms of hemoglobin call hemoglobin Bart or hemoglobin H. These abnormal hemoglobin molecules cannot effectively carry oxygen to the body's tissues. Substitution of Hb Bart or HbH for normal hemoglobin causes anemia and other serious health problems associated with alpha Thalassemia. Two additional variants of alpha Thalassemia are related to reduced amount of alpha-globin. Because cells still produce some normal hemoglobin, these variants tend to cause few or no health problems. Loss of two of four alpha-globin alleles results in alpha Thalassemia trait. People with the alpha Thalassemia trait may have unusually small, pale red blood cells and mild anemia.

* Please keep in mind that all text is machine-generated, we do not bear any responsibility, and you should always get advice from professionals before taking any actions.

* Please keep in mind that all text is machine-generated, we do not bear any responsibility, and you should always get advice from professionals before taking any actions

Epidemiology

The Frequency of BETA-THALASSEMIA mutations varies by regions of the world, with highest prevalence in the Mediterranean, Middle-East, and Southeast and Central Asia. Approximately 68000 children are born with BETA-THALASSEMIA. Its prevalence is of 80-90 million carriers, around 1. 5 % of the global population. Report carrier prevalence in Greek and Turkish populations in Cyprus is up to 15 %. Prevalence also parallels that of malaria as propose survival advantage provides selective pressure for high carrier frequency in these populations. Gene drift and founder effects are other reasons why THALASSEMIA is more frequent in areas mentioned above.

* Please keep in mind that all text is machine-generated, we do not bear any responsibility, and you should always get advice from professionals before taking any actions.

* Please keep in mind that all text is machine-generated, we do not bear any responsibility, and you should always get advice from professionals before taking any actions

Pathophysiology

Erythropoiesis in individuals with-THALASSEMIA reflect consequences of excess, unpaired-globin. Indeed, degree of imbalance in-globin versus +-globin biosynthetic ratio is MAJOR determinate of disease severity rather than underproduction of hemoglobin. In-THALASSEMIA trait there is twofold excess in synthesis of-globin, which is consistent with fairly normal hematopoiesis with only mild microcytosis and hypochromia of red cells. To non-biosynthetic ratio in Individuals with THALASSEMIA INTERMEDIA is typically 3-4 / 1 because residual capacity for-globin synthesis along with usually modest but variable-globin synthesis mitigate consequences of excess-globin production. Individuals with 0-THALASSEMIA mutations have mark chain biosynthetic imbalance as the underlying basis for their severe phenotype. Following synthesis,-globin interacts with its molecular chaperone,-hemoglobin stabilizing protein, to form protein complex before it is released to interact with-globin in forming hemoglobin tetramer. AHSP facilitates folding of-globin and prevents formation of misfolded aggregates.-Globin mutations that impair interaction with AHSP are associated with microcytosis and anemia in humans. Loss of AHSP has also been shown to impair erythropoiesis in mouse model of-THALASSEMIA. Evidence suggests that AHSP levels may influence the phenotype of-THALASSEMIA. Once the capacity of AHSP is exceed,-globin forms molecular aggregates, which precipitate, forming inclusions that damage cell membrane and membranes of intracellular organelles. Aggregate-chains also trigger formation of reactive oxygen species, which further damages protein and lipid constituents of cell membranes. As well as heme and iron, one of the most toxic products of unpaired-chains is hemichromes, which bind to membrane and promote clustering of band 3, one of its MAJOR constituents. Formation of-chain inclusions occurs early during erythropoiesis and peak in polychromatophilic erythroblasts, leading to cellular apoptosis. Thus, anemia in severe-thalassemias reflects both ineffective erythropoiesis as well as shortened red cell survival as a consequence of-globin inclusions. The Pathophysiology of-THALASSEMIA has been compared with other disorders such as Parkinsons Disease and Huntingtons Disease, which are caused by accumulations of unstable, aggregation-prone proteins. Almost all cells have some capacity to detoxify and remove damaging proteins via multiple biochemical pathways term protein quality control. Ubiquitin-proteasome system and lysosome-autophagy pathways that function in PQC are thought to participate in degradation of-globin, but capacities of these pathways are exceeded in erythroid cells of individuals with severe forms of-THALASSEMIA.

* Please keep in mind that all text is machine-generated, we do not bear any responsibility, and you should always get advice from professionals before taking any actions.

* Please keep in mind that all text is machine-generated, we do not bear any responsibility, and you should always get advice from professionals before taking any actions

History and Physical

Table

Cat. No.Item
5341Beta-Thal HbA2 Quik Column Kit, 50 tests
-50 HbA2 Quik Columns
-1 x 130 mL HbA2 Developer
-1 x 20 mL Hemolysate Reagent-C

THALASSEMIA is a blood disorder that is inherit. This means it is passed down from one or both parents through their genes. When you have THALASSEMIA, your body makes less hemoglobin than normal. Hemoglobin is an iron-rich protein in red blood cells. It carries oxygen to all parts of the body. There are two main types of THALASSEMIA: alpha and BETA. Different genes are affected by each type. THALASSEMIA can cause mild or severe anemia. Anemia occurs when your body does not have enough red blood cells or hemoglobin. Severity and type of anemia depends on how many genes are affect. BETA THALASSEMIA is caused by damage or missing genes. Two specific genes are involve. There are several types of this disorder: BETA THALASSEMIA MAJOR. There are two damaged genes. This is the most severe form of this disorder. People with this condition will need frequent blood transfusions. They may not live a normal lifespan. BETA THALASSEMIA minor or THALASSEMIA Trait. Only one gene is damage. This causes less severe anemia. People with this type have a 50 % chance of passing the gene to their children. If other parents are not affect, their children will also have this form of disorder. This type is further divided into: THALASSEMIA minima: There are few or no symptoms. THALASSEMIA INTERMEDIA: This causes moderate to severe anemia. Many people with this disorder are given iron replacement by mistake. This happens when lack of iron is believed to cause their anemia. Too much iron can be harmful. So it is important to get the right diagnosis. You may need to SEE a blood disorder specialist, call a hematologist. BETA THALASSEMIA is a Genetic Disease inherited from one or both parents. The only risk factor is having a family history of disease. Different people will have different symptoms, based on which type of disorder is inherit. BETA THALASSEMIA MAJOR: This is the most severe type of this disorder. Children born with this type will have symptoms early in life that include: pale skin Fussy Having poor appetite Having many infections Slow growth Belly swelling Yellowish skin without treatment, spleen, liver, and heart become enlarge. Bones can also become thin, brittle, and deform. People with this condition will need frequent blood transfusions and may not live a normal lifespan. Iron builds up in the heart and other organs from blood transfusions. This can cause heart failure as early as teens or early 20s. THALASSEMIA INTERMEDIA: This type can cause symptoms of moderate to severe anemia including: extreme tiredness, pale skin, slow or delayed growth Weak bones enlarge spleen BETA THALASSEMIA is most often found in people who are of Greek, Italian, African, or Asian origin. Diagnosis is most often make between 6 and 12 years old. These tests may be able to tell if you are carrier, and can pass disorder on to your children: complete blood count: This test checks the size, number, and maturity of different blood cells in a set volume of blood.

* Please keep in mind that all text is machine-generated, we do not bear any responsibility, and you should always get advice from professionals before taking any actions.

Table2

Cat. No.Item
5334Sickle-Thal Quik Column Kit, 25 tests
-25 Sickle-Thal Quik Columns
-1 x 130 mL HbA2 Developer
-1 x 300 mL HbS Developer
-1 x 20 mL Hemolysate-Reagent-C

Table3

Cat. No.Item
5339-HbA2 Quik Column Control-Normal, 5 x 1 mL
5333-HbA2 Quik Column Control-Abnormal, 5 x 1 mL
* Please keep in mind that all text is machine-generated, we do not bear any responsibility, and you should always get advice from professionals before taking any actions

Treatment / Management

Thalassemia has negative repercussions for many organs, and without a cure, it has high morbidity. The disorder is best managed by an interprofessional team that includes a Thalassemia care team, cardiologist, hepatologist, endocrinologist, and psychologist. Also, family care, nursing support, and social support are integral parts of management. A lead consultant should be in charge of patient care, and a nurse specialist, along with other specialists in respective fields, should be involved to cover all aspects of disease. Patient education is crucial, and social worker involvement, including geneticist, is essential. In some parts of the world, preventive strategies include prenatal screening, restrictions on issuing marriage licenses to two people with the same disease. Screening of children and pregnant women who visit clinicians is an effective strategy to limit disease morbidity. Social workers should ensure that the caregiver / patient has adequate support and financial resources so that they can continue with treatment. Nurses should educate patients on the importance of treatment compliance to avoid serious complications, as well as monitoring treatment progress. Pharmacists may soon play a greater role as there are new drug products to assist in gene therapy on the horizon that can eliminate the need for ongoing transfusions. Active collaboration and discussion between interprofessional team members help in better understanding of progression or control of disease.


Etiology

Reduced amount or absence of beta globin chains result in relative excess of unbound alpha globin chains that precipitate in erythroid precursors in bone marrow, leading to their premature death and hence to ineffective erythropoiesis. The degree of globin chain reduction is determined by the nature of mutation in beta globin gene located on chromosome 11. Peripheral hemolysis contributing to anemia is less prominent in thalassemia major than in thalassemia intermedia, and occurs when insoluble alpha globin chains induce membrane damage to peripheral erythrocytes. Anemia stimulates production of erythropoietin with consequent intensive but ineffective expansion of bone marrow, which in turn causes typical previously described bone deformities. Prolong and severe anemia and increased erythropoietic drive also result in hepatosplenomegaly and extramedullary erythropoiesis.

* Please keep in mind that all text is machine-generated, we do not bear any responsibility, and you should always get advice from professionals before taking any actions.

* Please keep in mind that all text is machine-generated, we do not bear any responsibility, and you should always get advice from professionals before taking any actions

Complications

Complications related to overstimulation of bone marrow, ineffective erythropoiesis, and iron overload from blood transfusions. Iron accumulates in the heart, causing heart failure, which is the most common cause of death in TM due to iron accumulation. Symptoms differ from nonanemic patients because of adaptation to chronic Anemia. Usually, these patients have dyspnea, with resting tachycardia, low blood pressure, high ejection fraction, and high cardiac output. Atrial fibrillation is another long-term complication of iron oxidative stress. According to several studies, it is more prevalent in TM patients than in the general population. Iron also accumulates in the endocrine glands, causing hypothyroidism, hypoparathyroidism, adrenal insufficiency, diabetes mellitus, and hypogonadism. Thromboembolic events such as deep venous thrombosis, pulmonary embolism, and recurrent arterial occlusion are more common in Thalassemia patients than in the normal population. This complication is due to chronic hypercoagulable state, particularly in Thalassemia Intermedia. They have low levels of protein C and protein S, increasing D-dimer levels. Other complications are chronic hepatitis, cirrhosis, hypersplenism, HIV infection, and osteoporosis.

* Please keep in mind that all text is machine-generated, we do not bear any responsibility, and you should always get advice from professionals before taking any actions.

* Please keep in mind that all text is machine-generated, we do not bear any responsibility, and you should always get advice from professionals before taking any actions

What Is Beta Thalassemia?

People inherit genes for beta Thalassemia from their parents. A child gets one beta protein gene from their mother and one from their father: someone who inherits gene change in beta protein from one parent has beta Thalassemia minor. Someone who inherits gene change in both beta proteins has beta Thalassemia intermedia or beta Thalassemia major. Sometimes beta Thalassemia gene change can be inherited with Sickle cell gene change. This results in Sickle beta Thalassemia, type of Sickle cell disease. Genetic counselor can help families understand different ways beta Thalassemia runs in families.

* Please keep in mind that all text is machine-generated, we do not bear any responsibility, and you should always get advice from professionals before taking any actions.

* Please keep in mind that all text is machine-generated, we do not bear any responsibility, and you should always get advice from professionals before taking any actions

Sources

* Please keep in mind that all text is machine-generated, we do not bear any responsibility, and you should always get advice from professionals before taking any actions.

* Please keep in mind that all text is machine-generated, we do not bear any responsibility, and you should always get advice from professionals before taking any actions

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