Beta-thalassemia overview: Difference between revisions
No edit summary |
|||
| (42 intermediate revisions by the same user not shown) | |||
| Line 1: | Line 1: | ||
__NOTOC__ | __NOTOC__ | ||
{{Beta-thalassemia}} | {{Beta-thalassemia}} | ||
{{CMG}} | {{CMG}}; {{AE}} {{MHP}} | ||
==Overview== | ==Overview== | ||
==Historical Perspective== | |||
The [[Thalassemia]] term was invented by a hematologist, Dr. Thomas Cooley, in 1925. It has a Greek origin and consists of Thalassa and Emia which mean sea and blood, respectively. The diagnostic certainty was ultimately established with hemoglobin electrophoresis in the 20th century. | |||
==Classification== | |||
Beta-Thalassemia is classified based on the severity and the type of responsible mutation. It mainly has 3 types: β thalassemia minor, β thalassemia major, Thalassemia intermedia. There are less common types such as E/Beta-thalassemia, autosomal dominant Beta-thalassemia and atypical Beta-Thalassemia. | |||
==Pathophysiology== | |||
Beta-Thalassemia is an inherited disorder in hemoglobulin production due to a variety of genetic mutations in the gene responsible for [[Beta-globin]] production (HBB gene, on chromosome 11). The effects of beta-thalassemia on red blood cell morphology and function are significantly detrimental. Beta-Thalassemia contributes to abnormal hemoglobin and red blood cells (RBCs) that have impaired function in efficient oxygen delivery to different body tissues, which is called the state of [[anemia]]. As mutated genes are passed down, the shortage of functional red blood cells begins affecting the body from early infancy, and the lifelong persistence of insufficiency in beta-globin production results in chronic [[anemia]]. [[Hepatosplenomegaly]], delayed developmental milestones, [[jaundice]], bone problems, and different infections might happen in early infancy. | |||
==Differentiating Beta-thalassemia from other Diseases== | |||
Beta-thalassemia may have similar features of other conditions such as [[iron deficiency anemia]], [[sideroblastic anemia]], [[Alpha-thalassemia]], other [[hemolytic anemia]] and other [[hemoglobinopathies]] including [[sickle cell anemia]]. To differentiate these conditions, history and physical examination, electrophoresis of [[hemoglobin]], [[DNA]] analysis and [[iron]] level assessments would be useful. | |||
==Epidemiology and Demographics== | |||
The prevalence of beta-thalassemia carrier is 1.5% of the world population which is mainly in regions with a historical association with [[malaria]], including the Mediterranean, Middle East, Central Asia, Indian subcontinent, and parts of Southeast Asia and Africa. The incidence of beta-thalassemia is 42,000 per year. It affects both males and females in a similar demographic manner. | |||
==Risk Factors== | |||
In general, positive family history and specific ethnicities are the major risk factors for beta-thalassemia. On the other hand, lack of awareness and education about the screening for beta-thalassemia, limited resources for screening programs and consanguineous marriages are contributing factors for increasing the risk of beta-thalassemia. | |||
==Natural History, Complications and Prognosis== | |||
Without regular [[blood transfusions]], affected individuals by major beta-thalassemia typically develop severe [[anemia]] and other complications such as [[pulmonary hypertension]], [[right heart failure]], [[iron overload]], infections early in life, while beta-thalassemia intermedia patients would have a variable clinical course, complications, and prognosis. Beta-thalassemia minor subjects would not have significant symptoms, while in some cases might have an increased risk for [[iron deficiency anemia]]. Iron overload complications happen in transfusion-dependent thalassemia. | |||
The [[prognosis]] of [[beta-thalassemia]] depends on the severity of the disease and the presence of complications such as [[iron overload-related]] complications and [[cardiovascular]] disorders. | |||
==Diagnosis== | |||
===History and Symptoms=== | |||
Patients with beta-thalassemia major may manifest with severe [[anemia]], failure to thrive, [[pallor]], [[jaundice]], [[abdominal enlargement]], [[fatigue]], recurrent fever attacks, [[growth retardation]] and poor muscle tone early in childhood. Multiple [[transfusions]] can cause [[arthritis]], [[abdominal pain]], bronzed or grayish skin, [[loss of libido]], hormonal imbalances, and [[cognitive]] problems. Intermedia variant patients might experience moderate [[anemia]], [[splenomegaly]], bone changes, and intermittent need for [[blood transfusions]] at different ages. Patients with beta-thalassemia minor are basically asymptomatic or have minor [[anemic]] symptoms. | |||
===Physical Examination=== | |||
In physical examination of patients with beta-thalassemia major, [[pallor]], [[jaundice]], [[hepatosplenomegaly]], frontal bossing, long bone abnormalities, skull expansion with frontal, malar, and nasal bridge prominences, maxillary hypertrophy, malocclusion of jaw, short trunk, [[genu valgum]], delayed sexual development, low blood pressure and irregular pulse may be noticeable. Beta-thalassemia minor does not have significant signs and manifestations. | |||
===Laboratory Findings=== | |||
The initial work-up for diagnosis of beta-thalassemia includes complete blood count and [[hemoglobin electrophoresis]] which may indicate low hemoglobin level, [[MCV]], MCH and high hemoglobin F and A2. For advanced assessment, there are other methods such as: high-performance [[liquid chromatography]] (HPLC), capillary zone electrophoresis (CE) systems, chorionic villus sample, [[amniotic fluid]] evaluation, DNA analysis, PCR and genome sequencing. | |||
===X Ray=== | |||
In X-ray evaluation, thinning of bones and expanded bone marrow spaces can be observed. | |||
===CT=== | |||
CT scan is not a routine work-up in beta-thalassemia. However, the abdominal CT scan may reveal [[Hepatosplenomegaly]] due to [[Extramedullary hematopoiesis]]. | |||
===MRI=== | |||
Abdominopelvic MRI can suggest [[hepatosplenomegaly]]. MRI with T2 star sequence is a particular sequence of MRI that specifically assesses for iron overload states. MRI with T2 star of the heart or liver can help determine the degree of iron overload. | |||
===Ultrasound=== | |||
Ultrasound is not a routine work-up in beta-thalassemia. However, the abdominal ultrasound may reveal [[Hepatosplenomegaly]] due to [[Extramedullary hematopoiesis]]. | |||
===Other Imaging Findings=== | |||
There are no other imaging findings for beta-thalassemia. | |||
===Other Diagnostic Studies=== | |||
[[Serum ferritin]] levels, liver function tests, and genetic testing to identify specific beta-thalassemia mutations are other diagnostic studies which may help to confirm the diagnosis. | |||
==Treatment== | |||
===Medical Therapy=== | |||
The mainstay of treatment for beta-thalassemia major is [[blood transfusion]]. [[Chelation therapy]] is also required to manage iron overload resulting from repeated transfusions. In less severe cases, folic acid supplementation may be recommended to support red blood cell production. Bone marrow transplantation is the only cure for thalassemia, and is indicated for patients with severe thalassemia major. Untreated thalassemia major eventually leads to death, usually by heart failure; therefore, birth screening is very important. | |||
In beta-thalassemia minor, a serum ferritin test can determine what their iron levels are and guide them to further treatment if necessary. | |||
===Surgery=== | |||
Surgical intervention is frequently required to guarantee optimum management of the accompanying morbidity in beta-thalassemia cases. The most prevalent types of surgical interventions associated with beta-thalassemia include [[splenectomy]], [[cholecystectomy]], leg ulcers, fractures, and extramedullary pseudotumor. | |||
===Primary Prevention=== | |||
Primary prevention strategies are carrier screening, genetic counseling, and prenatal testing to identify at-risk couples and provide appropriate guidance regarding family planning options. | |||
===Secondary Prevention=== | |||
Secondary prevention measures would be needed after the initiation of blood transfusions with regular monitoring of iron overload, maintaining appropriate transfusion and [[chelation therapy]] regimens, and managing potential complications such as infections or organ dysfunction. | |||
===Cost-Effectiveness of Therapy=== | |||
The long-term cost-effectiveness of therapy for beta-thalassemia major depends on factors such as access to healthcare resources, availability of blood products, affordability of [[chelation therapy]], and overall disease management. | |||
===Future or Investigational Therapies=== | |||
Promising future therapies for beta-thalassemia major include [[gene therapy]], [[stem cell transplantation]], and novel approaches targeting gene editing or gene regulation to enhance the production of functional beta-globin chains. | |||
{{reflist|2}} | |||
[[Category:Genetic disorders]] | |||
[[Category:Blood disorders]] | |||
[[Category:Disease]] | |||
{{WikiDoc Help Menu}} | |||
{{WikiDoc Sources}} | |||
{{reflist|2}} | {{reflist|2}} | ||
Latest revision as of 08:13, 25 August 2023
|
Beta-thalassemia Microchapters |
|
Diagnosis |
|---|
|
Treatment |
|
Case Studies |
|
Beta-thalassemia overview On the Web |
|
American Roentgen Ray Society Images of Beta-thalassemia overview |
|
Risk calculators and risk factors for Beta-thalassemia overview |
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Maryam Hadipour, M.D.[2]
Overview
Historical Perspective
The Thalassemia term was invented by a hematologist, Dr. Thomas Cooley, in 1925. It has a Greek origin and consists of Thalassa and Emia which mean sea and blood, respectively. The diagnostic certainty was ultimately established with hemoglobin electrophoresis in the 20th century.
Classification
Beta-Thalassemia is classified based on the severity and the type of responsible mutation. It mainly has 3 types: β thalassemia minor, β thalassemia major, Thalassemia intermedia. There are less common types such as E/Beta-thalassemia, autosomal dominant Beta-thalassemia and atypical Beta-Thalassemia.
Pathophysiology
Beta-Thalassemia is an inherited disorder in hemoglobulin production due to a variety of genetic mutations in the gene responsible for Beta-globin production (HBB gene, on chromosome 11). The effects of beta-thalassemia on red blood cell morphology and function are significantly detrimental. Beta-Thalassemia contributes to abnormal hemoglobin and red blood cells (RBCs) that have impaired function in efficient oxygen delivery to different body tissues, which is called the state of anemia. As mutated genes are passed down, the shortage of functional red blood cells begins affecting the body from early infancy, and the lifelong persistence of insufficiency in beta-globin production results in chronic anemia. Hepatosplenomegaly, delayed developmental milestones, jaundice, bone problems, and different infections might happen in early infancy.
Differentiating Beta-thalassemia from other Diseases
Beta-thalassemia may have similar features of other conditions such as iron deficiency anemia, sideroblastic anemia, Alpha-thalassemia, other hemolytic anemia and other hemoglobinopathies including sickle cell anemia. To differentiate these conditions, history and physical examination, electrophoresis of hemoglobin, DNA analysis and iron level assessments would be useful.
Epidemiology and Demographics
The prevalence of beta-thalassemia carrier is 1.5% of the world population which is mainly in regions with a historical association with malaria, including the Mediterranean, Middle East, Central Asia, Indian subcontinent, and parts of Southeast Asia and Africa. The incidence of beta-thalassemia is 42,000 per year. It affects both males and females in a similar demographic manner.
Risk Factors
In general, positive family history and specific ethnicities are the major risk factors for beta-thalassemia. On the other hand, lack of awareness and education about the screening for beta-thalassemia, limited resources for screening programs and consanguineous marriages are contributing factors for increasing the risk of beta-thalassemia.
Natural History, Complications and Prognosis
Without regular blood transfusions, affected individuals by major beta-thalassemia typically develop severe anemia and other complications such as pulmonary hypertension, right heart failure, iron overload, infections early in life, while beta-thalassemia intermedia patients would have a variable clinical course, complications, and prognosis. Beta-thalassemia minor subjects would not have significant symptoms, while in some cases might have an increased risk for iron deficiency anemia. Iron overload complications happen in transfusion-dependent thalassemia. The prognosis of beta-thalassemia depends on the severity of the disease and the presence of complications such as iron overload-related complications and cardiovascular disorders.
Diagnosis
History and Symptoms
Patients with beta-thalassemia major may manifest with severe anemia, failure to thrive, pallor, jaundice, abdominal enlargement, fatigue, recurrent fever attacks, growth retardation and poor muscle tone early in childhood. Multiple transfusions can cause arthritis, abdominal pain, bronzed or grayish skin, loss of libido, hormonal imbalances, and cognitive problems. Intermedia variant patients might experience moderate anemia, splenomegaly, bone changes, and intermittent need for blood transfusions at different ages. Patients with beta-thalassemia minor are basically asymptomatic or have minor anemic symptoms.
Physical Examination
In physical examination of patients with beta-thalassemia major, pallor, jaundice, hepatosplenomegaly, frontal bossing, long bone abnormalities, skull expansion with frontal, malar, and nasal bridge prominences, maxillary hypertrophy, malocclusion of jaw, short trunk, genu valgum, delayed sexual development, low blood pressure and irregular pulse may be noticeable. Beta-thalassemia minor does not have significant signs and manifestations.
Laboratory Findings
The initial work-up for diagnosis of beta-thalassemia includes complete blood count and hemoglobin electrophoresis which may indicate low hemoglobin level, MCV, MCH and high hemoglobin F and A2. For advanced assessment, there are other methods such as: high-performance liquid chromatography (HPLC), capillary zone electrophoresis (CE) systems, chorionic villus sample, amniotic fluid evaluation, DNA analysis, PCR and genome sequencing.
X Ray
In X-ray evaluation, thinning of bones and expanded bone marrow spaces can be observed.
CT
CT scan is not a routine work-up in beta-thalassemia. However, the abdominal CT scan may reveal Hepatosplenomegaly due to Extramedullary hematopoiesis.
MRI
Abdominopelvic MRI can suggest hepatosplenomegaly. MRI with T2 star sequence is a particular sequence of MRI that specifically assesses for iron overload states. MRI with T2 star of the heart or liver can help determine the degree of iron overload.
Ultrasound
Ultrasound is not a routine work-up in beta-thalassemia. However, the abdominal ultrasound may reveal Hepatosplenomegaly due to Extramedullary hematopoiesis.
Other Imaging Findings
There are no other imaging findings for beta-thalassemia.
Other Diagnostic Studies
Serum ferritin levels, liver function tests, and genetic testing to identify specific beta-thalassemia mutations are other diagnostic studies which may help to confirm the diagnosis.
Treatment
Medical Therapy
The mainstay of treatment for beta-thalassemia major is blood transfusion. Chelation therapy is also required to manage iron overload resulting from repeated transfusions. In less severe cases, folic acid supplementation may be recommended to support red blood cell production. Bone marrow transplantation is the only cure for thalassemia, and is indicated for patients with severe thalassemia major. Untreated thalassemia major eventually leads to death, usually by heart failure; therefore, birth screening is very important.
In beta-thalassemia minor, a serum ferritin test can determine what their iron levels are and guide them to further treatment if necessary.
Surgery
Surgical intervention is frequently required to guarantee optimum management of the accompanying morbidity in beta-thalassemia cases. The most prevalent types of surgical interventions associated with beta-thalassemia include splenectomy, cholecystectomy, leg ulcers, fractures, and extramedullary pseudotumor.
Primary Prevention
Primary prevention strategies are carrier screening, genetic counseling, and prenatal testing to identify at-risk couples and provide appropriate guidance regarding family planning options.
Secondary Prevention
Secondary prevention measures would be needed after the initiation of blood transfusions with regular monitoring of iron overload, maintaining appropriate transfusion and chelation therapy regimens, and managing potential complications such as infections or organ dysfunction.
Cost-Effectiveness of Therapy
The long-term cost-effectiveness of therapy for beta-thalassemia major depends on factors such as access to healthcare resources, availability of blood products, affordability of chelation therapy, and overall disease management.
Future or Investigational Therapies
Promising future therapies for beta-thalassemia major include gene therapy, stem cell transplantation, and novel approaches targeting gene editing or gene regulation to enhance the production of functional beta-globin chains.