Alpha-thalassemia Mental Retardation Syndrome
   HOME

TheInfoList



OR:

Alpha-thalassemia (α-thalassemia, α-thalassaemia) is an inherited blood disorder and a form of
thalassemia Thalassemias are a group of Genetic disorder, inherited blood disorders that manifest as the production of reduced hemoglobin. Symptoms depend on the type of thalassemia and can vary from none to severe, including death. Often there is mild to ...
. Thalassemias are a group of inherited blood conditions which result in the impaired production of
hemoglobin Hemoglobin (haemoglobin, Hb or Hgb) is a protein containing iron that facilitates the transportation of oxygen in red blood cells. Almost all vertebrates contain hemoglobin, with the sole exception of the fish family Channichthyidae. Hemoglobin ...
, the molecule that carries
oxygen Oxygen is a chemical element; it has chemical symbol, symbol O and atomic number 8. It is a member of the chalcogen group (periodic table), group in the periodic table, a highly reactivity (chemistry), reactive nonmetal (chemistry), non ...
in the blood. Symptoms depend on the extent to which hemoglobin is deficient, and include
anemia Anemia (also spelt anaemia in British English) is a blood disorder in which the blood has a reduced ability to carry oxygen. This can be due to a lower than normal number of red blood cells, a reduction in the amount of hemoglobin availabl ...
,
pallor Pallor is a pale color of the skin that can be caused by illness, emotional shock or stress, stimulant use, or anemia, and is the result of a reduced amount of oxyhaemoglobin and may also be visible as pallor of the conjunctivae of the eye ...
,
tiredness Fatigue is a state of tiredness (which is not sleepiness), exhaustion or loss of energy. It is a symptom of any of various diseases; it is not a disease in itself. Fatigue (in the medical sense) is sometimes associated with medical conditions ...
, enlargement of the spleen,
iron overload Iron overload is the abnormal and increased accumulation of total iron in the body, leading to organ damage. The primary mechanism of organ damage is oxidative stress, as elevated intracellular iron levels increase free radical formation via the ...
, abnormal bone structure,
jaundice Jaundice, also known as icterus, is a yellowish or, less frequently, greenish pigmentation of the skin and sclera due to high bilirubin levels. Jaundice in adults is typically a sign indicating the presence of underlying diseases involving ...
, and
gallstones A gallstone is a stone formed within the gallbladder from precipitated bile components. The term cholelithiasis may refer to the presence of gallstones or to any disease caused by gallstones, and choledocholithiasis refers to the presence of ...
. In severe cases death ensues, often in infancy, or death of the unborn fetus. The disease is characterised by reduced production of the alpha-globin component of hemoglobin, caused by inherited mutations affecting the genes ''
HBA1 Hemoglobin subunit alpha, Hemoglobin, alpha 1, is a hemoglobin protein that in humans is encoded by the ''HBA1'' gene. Gene The human alpha globin gene cluster located on chromosome 16 spans about 30 kb and includes seven loci: 5'- zeta - pse ...
'' and ''
HBA2 Hemoglobin, alpha 2 also known as ''HBA2'' is a gene that in humans codes for the alpha globin chain of hemoglobin. Function The human alpha globin gene cluster is located on chromosome 16 and spans about 30 kb, including seven alpha like glo ...
.'' This causes reduced levels of hemoglobin leading to anemia, while the accumulation of surplus
beta-globin Hemoglobin subunit beta (beta globin, β-globin, haemoglobin beta, hemoglobin beta) is a globin protein, coded for by the ''HBB'' gene, which along with alpha globin (HBA1, HBA), makes up the most common form of haemoglobin in adult humans, hem ...
, the other structural component of hemoglobin, damages
red blood cells Red blood cells (RBCs), referred to as erythrocytes (, with -''cyte'' translated as 'cell' in modern usage) in academia and medical publishing, also known as red cells, erythroid cells, and rarely haematids, are the most common type of blood cel ...
and shortens their life. Diagnosis is by checking the medical history of near relatives, microscopic examination of
blood smear A blood smear, peripheral blood smear or blood film is a thin layer of blood smeared on a glass microscope slide and then stained in such a way as to allow the various blood cells to be examined microscopically. Blood smears are examined in the i ...
,
ferritin Ferritin is a universal intracellular and extracellular protein that stores iron and releases it in a controlled fashion. The protein is produced by almost all living organisms, including archaea, bacteria, algae, higher plants, and animals. ...
test,
hemoglobin electrophoresis Hemoglobin electrophoresis is a blood test that can detect different types of hemoglobin. The test can detect hemoglobin S, the form associated with sickle cell disease, as well as other abnormal types of hemoglobin, such as hemoglobin C. It can ...
, and
DNA sequencing DNA sequencing is the process of determining the nucleic acid sequence – the order of nucleotides in DNA. It includes any method or technology that is used to determine the order of the four bases: adenine, thymine, cytosine, and guanine. The ...
. As an inherited condition, alpha thalassemia cannot be prevented although
genetic counselling Genetic may refer to: *Genetics, in biology, the science of genes, heredity, and the variation of organisms **Genetic, used as an adjective, refers to genes ***Genetic disorder, any disorder caused by a genetic mutation, whether inherited or de nov ...
of parents prior to conception can propose the use of donor sperm or
eggs An egg is an organic vessel in which an embryo begins to develop. Egg, EGG or eggs may also refer to: Biology * Egg cell, the female reproductive cell (gamete) in oogamous organisms Food * Eggs as food Places * Egg, Austria * Egg, Switzerland ...
. The principle form of management is blood transfusion every 3 to 4 weeks, which relieves the anemia but leads to iron overload and possible
immune reaction An immune response is a physiological reaction which occurs within an organism in the context of inflammation for the purpose of defending against exogenous factors. These include a wide variety of different toxins, viruses, intra- and extracellula ...
. Medication includes
folate Folate, also known as vitamin B9 and folacin, is one of the B vitamins. Manufactured folic acid, which is converted into folate by the body, is used as a dietary supplement and in food fortification as it is more stable during processing and ...
supplementation,
iron chelation Chelation therapy is a medical procedure that involves the administration of chelating agents to remove heavy metals from the body. Chelation therapy has a long history of use in clinical toxicology and remains in use for some very specific medica ...
,
bisphosphonates Bisphosphonates are a class of drugs that prevent the loss of bone density, used to treat osteoporosis and similar diseases. They are the most commonly prescribed to treat osteoporosis. Evidence shows that they reduce the risk of fracture in p ...
, and removal of the spleen. Alpha thalassemia can also be treated by
bone marrow transplant Hematopoietic stem-cell transplantation (HSCT) is the transplantation of multipotent hematopoietic stem cells, usually derived from bone marrow, peripheral blood, or umbilical cord blood, in order to replicate inside a patient and produce a ...
from a well matched donor. Thalassemias were first identified in severely sick children in 1925, with identification of alpha and beta subtypes in 1965. Alpha thalassemia has its greatest prevalence in populations originating from Southeast Asia, Mediterranean countries, Africa, the Middle East, India, and Central Asia. Having a mild form of alpha thalassemia has been demonstrated to protect against malaria and thus can be an advantage in malaria
endemic Endemism is the state of a species being found only in a single defined geographic location, such as an island, state, nation, country or other defined zone; organisms that are indigenous to a place are not endemic to it if they are also foun ...
areas.


Cause

Alpha-thalassemia is almost always inherited. It is a
recessive In genetics, dominance is the phenomenon of one variant (allele) of a gene on a chromosome masking or overriding the effect of a different variant of the same gene on the other copy of the chromosome. The first variant is termed dominant and ...
trait - a single defective gene is insufficient to cause illness. Due to the involvement of four alpha globin genes, the inheritance pattern is complex, with varying severity depending on the number of gene mutations inherited from each parent. Normal individuals carry 4 alpha-globin genes, comprising
autosomal An autosome is any chromosome that is not a sex chromosome. The members of an autosome pair in a diploid cell have the same morphology, unlike those in allosomal (sex chromosome) pairs, which may have different structures. The DNA in autosome ...
pairs of the HBA1 and HBA2 genes. There are approximately 130 known mutations which can cause alpha thalassemia, mainly comprising deletion of part or all of a gene which then fails to produce alpha globin. If either one gene or two out of the four is faulty, the remaining genes produce sufficient alpha globin for normal life. If three genes are faulty, the sole functioning gene produces relatively small quantities of alpha globin, causing anemia and HbH disease. Four faulty genes (and therefore zero alpha globin) is incompatible with life. In rare cases alpha thalassemia can be acquired as a consequence of myelodysplastic cancer.


Pathophysiology


Symptoms

Symptoms depend on the type and severity of thalassemia. Carriers of thalassemia genes may have no symptoms or very mild symptoms with occasional crisis; those with three or more (out of four) affected genes will have severe and life threatening symptoms. Full alpha thalassemia with all four genes failing to synthesise alpha-globin, is generally fatal to the unborn child. The absence of alpha globin means that zero functional hemoglobin is produced during gestation. Unmatched gamma globin chains cluster to form hemoglobin Bart's, which is ineffective at transporting oxygen. In this situation, a fetus will develop
hydrops fetalis Hydrops fetalis or hydrops foetalis is a condition in the fetus characterized by an accumulation of fluid, or edema, in at least two fetal compartments. By comparison, hydrops allantois or hydrops amnion is an accumulation of excessive fluid in ...
, a form of
edema Edema (American English), also spelled oedema (British English), and also known as fluid retention, swelling, dropsy and hydropsy, is the build-up of fluid in the body's tissue (biology), tissue. Most commonly, the legs or arms are affected. S ...
, which can be detected on prenatal ultrasound. The child will normally die before or shortly after birth, unless intrauterine
blood transfusion Blood transfusion is the process of transferring blood products into a person's Circulatory system, circulation intravenously. Transfusions are used for various medical conditions to replace lost components of the blood. Early transfusions used ...
is performed. Less severe alpha thalassemia may affect growth and development. If thalassemia is untreated or undetected in the infant, this can lead to developmental issues such as slowed growth, delayed puberty, bone abnormalities, and intellectual impairment. More generally, impaired production of hemoglobin causes
anemia Anemia (also spelt anaemia in British English) is a blood disorder in which the blood has a reduced ability to carry oxygen. This can be due to a lower than normal number of red blood cells, a reduction in the amount of hemoglobin availabl ...
, resulting in tiredness and a general lack of energy, shortness of breath, rapid or irregular heartbeat, dizziness, pale skin, yellowing of the skin and eyes (jaundice). In thalassemia, ineffective
erythropoiesis Erythropoiesis (from Greek ''erythro'', meaning ''red'' and ''poiesis'', meaning ''to make'') is the process which produces red blood cells (erythrocytes), which is the development from erythropoietic stem cell to mature red blood cell. It is s ...
causes the bone marrow to expand. This expansion is a compensatory response to the damage caused to red blood cells by the imbalanced production of globin chains. Bone marrow expansion can lead to abnormal bone structure, particularly in the skull and face. Expansion of the bone marrow in the developing child leads to a distinctive facial shape often referred to as "Chipmunk
facies In geology, a facies ( , ; same pronunciation and spelling in the plural) is a body of rock with distinctive characteristics. The characteristics can be any observable attribute of rocks (such as their overall appearance, composition, or con ...
". Other skeletal changes include
osteoporosis Osteoporosis is a systemic skeletal disorder characterized by low bone mass, micro-architectural deterioration of bone tissue leading to more porous bone, and consequent increase in Bone fracture, fracture risk. It is the most common reason f ...
,
growth retardation A delayed milestone, which is also known as a developmental delay, refers to a situation where a child does not reach a particular developmental milestone at the expected age. Developmental milestones refer to a collection of indicators that a chil ...
, and malformation of the spine. People with thalassemia can get too much iron in their bodies, either from the disease itself as RBCs are destroyed, or as a consequence of frequent blood transfusions. Excess iron is not excreted, but forms toxic non-transferrin-bound iron. This can lead to organ damage, potentially affecting the heart, liver, endocrine system, bones and spleen. Symptoms include an irregular heartbeat,
cardiomyopathy Cardiomyopathy is a group of primary diseases of the heart muscle. Early on there may be few or no symptoms. As the disease worsens, shortness of breath, feeling tired, and swelling of the legs may occur, due to the onset of heart failure. A ...
,
cirrhosis Cirrhosis, also known as liver cirrhosis or hepatic cirrhosis, chronic liver failure or chronic hepatic failure and end-stage liver disease, is a chronic condition of the liver in which the normal functioning tissue, or parenchyma, is replaced ...
of the liver,
hypothyroidism Hypothyroidism is an endocrine disease in which the thyroid gland does not produce enough thyroid hormones. It can cause a number of symptoms, such as cold intolerance, poor ability to tolerate cold, fatigue, extreme fatigue, muscle aches, co ...
, delayed
puberty Puberty is the process of physical changes through which a child's body matures into an adult body capable of sexual reproduction. It is initiated by hormonal signals from the brain to the gonads: the ovaries in a female, the testicles i ...
and fertility problems, brittle and deformed bones, and an enlarged spleen. The
spleen The spleen (, from Ancient Greek '' σπλήν'', splḗn) is an organ (biology), organ found in almost all vertebrates. Similar in structure to a large lymph node, it acts primarily as a blood filter. The spleen plays important roles in reg ...
is the organ which removes damaged red blood cells from circulation; in thalassemia patients it is abnormally active, causing it to enlarge and possibly become hyperactive, a condition called
hypersplenism Splenomegaly is an enlargement of the spleen. The spleen usually lies in the left upper quadrant (LUQ) of the human abdomen. Splenomegaly is one of the four cardinal signs of ''hypersplenism'' which include: some reduction in number of circulatin ...
. The
immune system The immune system is a network of biological systems that protects an organism from diseases. It detects and responds to a wide variety of pathogens, from viruses to bacteria, as well as Tumor immunology, cancer cells, Parasitic worm, parasitic ...
can become compromised in a number of ways; anemia, iron overload, and hypersplenism may affect the immune response and increase the risk of severe infection.


Diagnosis


Prognosis

The prognosis for alpha thalassemia depends on the degree to which alpha globin production is affected. Those with mild alpha thalassemia, involving deletion of one or two alpha-globin genes, do not generally require treatment and have a normal life expectancy. Hemoglobin H disease, with three of the four genes either deleted or inactive, gives a mild to moderate form of anemia but may lead normal lives. The prognosis when all four genes are affected, leading to Hb Bart's
hydrops fetalis Hydrops fetalis or hydrops foetalis is a condition in the fetus characterized by an accumulation of fluid, or edema, in at least two fetal compartments. By comparison, hydrops allantois or hydrops amnion is an accumulation of excessive fluid in ...
, is very poor, with most affected fetuses dying ''
in utero The uterus (from Latin ''uterus'', : uteri or uteruses) or womb () is the organ in the reproductive system of most female mammals, including humans, that accommodates the embryonic and fetal development of one or more fertilized eggs until bir ...
'' or shortly after birth due to severe
fetal hypoxia Intrauterine hypoxia (also known as fetal hypoxia) occurs when the fetus is deprived of an adequate supply of oxygen. It may be due to a variety of reasons such as prolapse or occlusion of the umbilical cord, placental infarction, maternal dia ...
. It can be treated with intrauterine transfusions, however survival remains low and the infant requires lifelong blood transfusions. As of 2017, 69 patients were known who have survived past infancy.


Treatment

Treatment for thalassemia depends on the severity of the disease. People with thalassemia
traits Trait may refer to: * Phenotypic trait in biology, which involve genes and characteristics of organisms * Genotypic trait, sometimes but not always presenting as a phenotypic trait * Personality, traits that predict an individual's behavior. ** ...
(thalassemia minor or non transfusion dependent thalassemia), may not require medical or follow-up care after the initial diagnosis is made. Occasionally transfusions may be necessary particularly around childbirth, surgery, or if other conditions provoke anemia. A folic acid supplement may also be recommended. For those with severe forms of thalassemia (thalassemia major, or transfusion-dependent thalassemia), the three principal treatments are red blood cell transfusions to relieve anemia, iron chelation to mitigate the side effects of transfusion, and folic acid supplementation to encourage the growth of new blood cells. Other forms of treatment available depending on individual circumstances.


Red blood cell transfusions

Blood transfusions Blood transfusion is the process of transferring blood products into a person's circulation intravenously. Transfusions are used for various medical conditions to replace lost components of the blood. Early transfusions used whole blood, but ...
are the main treatment approach for prolonging life. Donated healthy red blood cells have a functional life of 4 to 6 weeks before they wear out and are broken down in the spleen. Regular transfusions every three to four weeks are necessary in order to maintain hemoglobin at a healthy level. Transfusions come with risks including
iron overload Iron overload is the abnormal and increased accumulation of total iron in the body, leading to organ damage. The primary mechanism of organ damage is oxidative stress, as elevated intracellular iron levels increase free radical formation via the ...
, the risk of acquiring infections, and the risk of immune reaction to the donated cells (
alloimmunization Alloimmunity (sometimes called isoimmunity) is an immune response to nonself antigens from members of the same species, which are called alloantigens or isoantigens. Two major types of alloantigens are blood group antigens and histocompatibility a ...
).


Iron chelation

Multiple blood transfusions lead to severe
iron overload Iron overload is the abnormal and increased accumulation of total iron in the body, leading to organ damage. The primary mechanism of organ damage is oxidative stress, as elevated intracellular iron levels increase free radical formation via the ...
, as the body eventually breaks down the hemoglobin in donated cells. This releases iron which it is unable to excrete. Iron overload may be treated by
chelation therapy Chelation therapy is a medical procedure that involves the administration of chelating agents to remove heavy metals from the body. Chelation therapy has a long history of use in clinical toxicology and remains in use for some very specific medic ...
with the medications
deferoxamine Deferoxamine (DFOA), also known as desferrioxamine and sold under the brand name Desferal, is a medication that binds iron and aluminium. It is specifically used in iron overdose, hemochromatosis either due to multiple blood transfusions or an ...
,
deferiprone Deferiprone, sold under the brand name Ferriprox among others, is a medication that chelates iron and is used to treat iron overload in thalassaemia major. It was first approved and indicated for use in treating thalassaemia major in 1994 and ...
, or
deferasirox Deferasirox, sold under the brand name Exjade among others, is an oral iron chelator. Its main use is to reduce chronic iron overload in patients who are receiving long-term blood transfusions for conditions such as beta-thalassemia and other ...
.
Deferoxamine Deferoxamine (DFOA), also known as desferrioxamine and sold under the brand name Desferal, is a medication that binds iron and aluminium. It is specifically used in iron overdose, hemochromatosis either due to multiple blood transfusions or an ...
is only effective as a daily injection, complicating its long-term use. Adverse effects include primary skin reactions around the injection site and
hearing loss Hearing loss is a partial or total inability to hear. Hearing loss may be present at birth or acquired at any time afterwards. Hearing loss may occur in one or both ears. In children, hearing problems can affect the ability to acquire spo ...
. Deferasirox and deferiprone are both oral medications, whose common side effects include nausea, vomiting and diarrhea.


Folic acid

Folate Folate, also known as vitamin B9 and folacin, is one of the B vitamins. Manufactured folic acid, which is converted into folate by the body, is used as a dietary supplement and in food fortification as it is more stable during processing and ...
is a B group vitamin which is involved in the manufacture of red blood cells. Folate supplementation, in the form of folic acid, is often recommended in thalassemia.


Osteoporosis

People with thalassemia are at a higher risk of
osteoporosis Osteoporosis is a systemic skeletal disorder characterized by low bone mass, micro-architectural deterioration of bone tissue leading to more porous bone, and consequent increase in Bone fracture, fracture risk. It is the most common reason f ...
. Treatment options include
bisphosphonates Bisphosphonates are a class of drugs that prevent the loss of bone density, used to treat osteoporosis and similar diseases. They are the most commonly prescribed to treat osteoporosis. Evidence shows that they reduce the risk of fracture in p ...
and
zinc supplementation Zinc deficiency is defined either as insufficient body levels of zinc to meet the needs of the body, or as a zinc blood level below the normal range. However, since a decrease in blood concentration is only detectable after long-term or severe ...
.


Removal of the spleen

The spleen is the organ which removes damaged or misshapen red blood cells from the circulation. In thalassemia, this can lead to the spleen becoming enlarged, a condition known as
splenomegaly Splenomegaly is an enlargement of the spleen. The spleen usually lies in the left upper quadrant (LUQ) of the human abdomen. Splenomegaly is one of the four cardinal signs of ''hypersplenism'' which include: some reduction in number of circulat ...
. Slight enlargement of the spleen is not a problem, however if it becomes extreme then surgical removal of the spleen (splenectomy) may be recommended.


Hematopoietic stem cell transplantation

Hematopoietic stem cell transplantation Hematopoietic stem-cell transplantation (HSCT) is the transplantation of multipotent hematopoietic stem cells, usually derived from bone marrow, peripheral blood, or umbilical cord blood, in order to replicate inside a patient and produce ...
(HSCT) is a potentially curative treatment for both alpha and beta thalassemia. It involves replacing the dysfunctional
stem cells In multicellular organisms, stem cells are undifferentiated or partially differentiated cells that can change into various types of cells and proliferate indefinitely to produce more of the same stem cell. They are the earliest type of cell ...
in the bone marrow with healthy cells from a well-matched
donor A donor in general is a person, organization or government which donates something voluntarily. The term is usually used to represent a form of pure altruism, but is sometimes used when the payment for a service is recognized by all parties as re ...
. Cells are ideally sourced from
human leukocyte antigen The human leukocyte antigen (HLA) system is a complex of genes on chromosome 6 in humans that encode cell-surface proteins responsible for regulation of the immune system. The HLA system is also known as the human version of the major histo ...
matched relatives; the procedure is more likely to succeed in children rather than adults. The first HSC transplant for thalassemia was carried out in 1981 on a patient with beta thalassemia major. Since then, a number of patients have received bone marrow transplants from healthy matched donors, although this procedure has a high level of risk. In 2018 an unborn child with
hydrops fetalis Hydrops fetalis or hydrops foetalis is a condition in the fetus characterized by an accumulation of fluid, or edema, in at least two fetal compartments. By comparison, hydrops allantois or hydrops amnion is an accumulation of excessive fluid in ...
, a potentially fatal complication of alpha thalassemia, was successfully transfused ''
in utero The uterus (from Latin ''uterus'', : uteri or uteruses) or womb () is the organ in the reproductive system of most female mammals, including humans, that accommodates the embryonic and fetal development of one or more fertilized eggs until bir ...
'' with her mother's stem cells. HSCT is a dangerous procedure with many possible complications; it is reserved for patients with life-threatening diseases. Risks associated with HSCT can include graft-versus host disease, failure of the graft, and other toxicity related to the transplant. In one study of 31 people, the procedure was successful for 22 whose hemoglobin levels improved to the normal range, in seven the graft failed and they continued to live with thalassemia, and two died of transplantation-related causes.


Evolutionary advantage

Some hemoglobinopathies seem to have given an evolutionary benefit, especially to
heterozygotes Zygosity (the noun, zygote, is from the Greek "yoked," from "yoke") () is the degree to which both copies of a chromosome or gene have the same genetic sequence. In other words, it is the degree of similarity of the alleles in an organism. Mos ...
, in areas where
malaria Malaria is a Mosquito-borne disease, mosquito-borne infectious disease that affects vertebrates and ''Anopheles'' mosquitoes. Human malaria causes Signs and symptoms, symptoms that typically include fever, Fatigue (medical), fatigue, vomitin ...
is
endemic Endemism is the state of a species being found only in a single defined geographic location, such as an island, state, nation, country or other defined zone; organisms that are indigenous to a place are not endemic to it if they are also foun ...
. Having a mild form of alpha thalassemia has been demonstrated to protect against malaria and thus can be an advantage in malaria endemic areas, thus conferring a selective survival advantage on carriers (known as
heterozygous advantage A heterozygote advantage describes the case in which the heterozygous genotype has a higher relative fitness than either the homozygous dominant or homozygous recessive genotype. Loci exhibiting heterozygote advantage are a small minority of lo ...
), and perpetuating the mutation. Alpha thalassemia genes have a high prevalence in populations originating in
sub-Saharan Africa Sub-Saharan Africa is the area and regions of the continent of Africa that lie south of the Sahara. These include Central Africa, East Africa, Southern Africa, and West Africa. Geopolitically, in addition to the list of sovereign states and ...
,
Mediterranean The Mediterranean Sea ( ) is a sea connected to the Atlantic Ocean, surrounded by the Mediterranean basin and almost completely enclosed by land: on the east by the Levant in West Asia, on the north by Anatolia in West Asia and Southern ...
,
Middle East The Middle East (term originally coined in English language) is a geopolitical region encompassing the Arabian Peninsula, the Levant, Turkey, Egypt, Iran, and Iraq. The term came into widespread usage by the United Kingdom and western Eur ...
, and
southeast The points of the compass are a set of horizontal, Radius, radially arrayed compass directions (or Azimuth#In navigation, azimuths) used in navigation and cartography. A ''compass rose'' is primarily composed of four cardinal directions—north, ...
and
east Asia East Asia is a geocultural region of Asia. It includes China, Japan, Mongolia, North Korea, South Korea, and Taiwan, plus two special administrative regions of China, Hong Kong and Macau. The economies of Economy of China, China, Economy of Ja ...
; all areas which historically have been malaria endemic. The prevalence of these genes has increased in previously non-endemic areas as a consequence of migration flows, slave-trade, and colonization. A number of mechanisms have been proposed to explain the increased chance of survival for the carrier of an abnormal hemoglobin trait.


Combination hemoglobinopathies

A combination hemoglobinopathy occurs when someone inherits two different abnormal hemoglobin genes. Alpha thalassemia can coexist with other hemoglobinopathies such as
sickle cell disease Sickle cell disease (SCD), also simply called sickle cell, is a group of inherited Hemoglobinopathy, haemoglobin-related blood disorders. The most common type is known as sickle cell anemia. Sickle cell anemia results in an abnormality in the ...
and
beta thalassemia Beta-thalassemia (β-thalassemia) is an genetic disorder, inherited hemoglobinopathy, blood disorder, a form of thalassemia resulting in variable outcomes ranging from clinically asymptomatic to severe anemia individuals. It is caused by reduce ...
. When alpha thalassemia carrier or trait combines with another hemoglobinopathy, the symptoms are generally those of the other .


See also

*
Thalassemia Thalassemias are a group of Genetic disorder, inherited blood disorders that manifest as the production of reduced hemoglobin. Symptoms depend on the type of thalassemia and can vary from none to severe, including death. Often there is mild to ...
*
Beta-thalassemia Beta-thalassemia (β-thalassemia) is an inherited blood disorder, a form of thalassemia resulting in variable outcomes ranging from clinically asymptomatic to severe anemia individuals. It is caused by reduced or absent synthesis of the beta ...
*
Delta-thalassemia Delta-beta thalassemia is a rare form of thalassemia in which there is a reduced production of HBD, hemoglobin subunit delta and hemoglobin subunit beta and raised levels of HBG1, hemoglobin subunit gamma. It is an autosomal recessive disorder. Si ...
*
Hemoglobinopathy Hemoglobinopathy is the medical term for a group of inherited blood disorders involving the hemoglobin, the major protein of red blood cells. They are generally single-gene disorders and, in most cases, they are inherited as Autosome, autosomal R ...


References


Further reading

* *


External links

* {{DEFAULTSORT:Alpha-Thalassemia Disorders of globin and globulin proteins Hereditary hemolytic anemias