Alpha-thalassemia (α-thalassemia, α-thalassaemia) is a form of
thalassemia
Thalassemias are inherited blood disorders characterized by decreased hemoglobin production. Symptoms depend on the type and can vary from none to severe. Often there is mild to severe anemia (low red blood cells or hemoglobin). Anemia can resul ...
involving 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 - pseu ...
''
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 globin ...
''. Thalassemias are a group of
inherited blood conditions which result in the impaired production of
hemoglobin
Hemoglobin (haemoglobin BrE) (from the Greek word αἷμα, ''haîma'' 'blood' + Latin ''globus'' 'ball, sphere' + ''-in'') (), abbreviated Hb or Hgb, is the iron-containing oxygen-transport metalloprotein present in red blood cells (erythrocyte ...
, the molecule that carries oxygen in the blood. Normal hemoglobin consists of two
alpha chains and two
beta chains; in alpha-thalassemia, there is a quantitative decrease in the amount of alpha chains, resulting in fewer normal hemoglobin molecules. Furthermore, alpha-thalassemia leads to the production of unstable beta globin molecules which cause increased
red blood cell
Red blood cells (RBCs), also referred to as red cells, red blood corpuscles (in humans or other animals not having nucleus in red blood cells), haematids, erythroid cells or erythrocytes (from Greek ''erythros'' for "red" and ''kytos'' for "holl ...
destruction. The degree of impairment is based on which clinical
phenotype
In genetics, the phenotype () is the set of observable characteristics or traits of an organism. The term covers the organism's morphology or physical form and structure, its developmental processes, its biochemical and physiological prop ...
is present (how many genes are affected).
[
]
Signs and symptoms
The presentation of individuals with alpha-thalassemia consists of:
Cause
Alpha-thalassemias are most commonly inherited in a Mendelian
Mendelian inheritance (also known as Mendelism) is a type of biological inheritance following the principles originally proposed by Gregor Mendel in 1865 and 1866, re-discovered in 1900 by Hugo de Vries and Carl Correns, and later populari ...
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 ...
manner. They are also associated with deletions of chromosome 16
Chromosome 16 is one of the 23 pairs of chromosomes in humans. People normally have two copies of this chromosome. Chromosome 16 spans about 90 million base pairs (the building material of DNA) and represents just under 3% of the total DNA in ce ...
p. Alpha thalassemia can also be acquired under rare circumstances.
Pathophysiology
The mechanism sees that α thalassemias results in decreased alpha-globin production, therefore fewer alpha-globin chains are produced, resulting in an excess of β chains in adults and excess γ chains in newborns. The excess β chains form unstable tetramers called hemoglobin H or HbH of four beta chains. The excess γ chains form tetramers which are poor carriers of O2 since their affinity for O2 is too high, so it is not dissociated in the periphery. Homozygote
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.
Mo ...
α0 thalassaemias, where numerous γ4 but no α-globins occur at all (referred to as Hb Barts), often result in death soon after birth.
Diagnosis
Diagnosis of alpha-thalassemia is primarily by laboratory evaluation and molecular diagnosis. Alpha-thalassemia can be mistaken for iron-deficiency anaemia on a full blood count or blood film, as both conditions have a microcytic anaemia. Serum iron
Serum iron is a medical laboratory test that measures the amount of circulating iron that is bound to transferrin (90%) and serum ferritin (10%). Clinicians order this laboratory test when they are concerned about iron deficiency, which can cause a ...
and serum ferritin can be used to exclude iron-deficiency anaemia.
Types
Two genetic loci exist for α globin, thus four alleles are in diploid cells. Two alleles are maternal and two alleles are paternal in origin. The severity of the α-thalassemias is correlated with the number of affected α-globin alleles: the greater, the more severe will be the manifestations of the disease. When noting the genotype, an "α" indicates a functional alpha chain, and '-' a pathological one.[
]
Laboratory diagnosis
The ability to measure hemoglobin Barts makes it useful in newborn screening tests. If hemoglobin Barts is detected on a newborn screen, the patient is usually referred for further evaluation since detection of hemoglobin Barts can indicate either one alpha globin gene deletion, making the baby a silent alpha thalassemia carrier, two alpha globin gene deletions (alpha thalassemia), or hemoglobin H disease
Hemoglobin H disease is a type of alpha thalassemia caused by impaired production of three of the four alpha globins, coded by genes HBA1 and HBA2.
See also
* Hemoglobin Barts Hemoglobin Barts, abbreviated Hb Barts, is an abnormal type of hemo ...
(three alpha globin gene deletions).
Deletion of four alpha globin genes was previously felt to be incompatible with life, but there are currently 69 patients who have survived past infancy. All such children too show high level of hemoglobin Barts on newborn screen along with other variants.
Post-newborn ages, initial laboratory diagnosis should include a complete blood count
A complete blood count (CBC), also known as a full blood count (FBC), is a set of medical laboratory tests that provide information about the cells in a person's blood. The CBC indicates the counts of white blood cells, red blood cells and ...
and red blood cell indices. As well, a peripheral 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 ...
should be carefully reviewed. In hemoglobin H disease, red blood cells containing hemoglobin H inclusions can be visualized on the blood smear using new methylene blue
is an organic compound of the thiazine class of heterocycles. It is used as a stain and as an antimicrobial agent. It is classified as an azine dye, and the chromophore is a cation, the anion is often unspecified.
Applications
NMB is a stainin ...
or brilliant cresyl blue stain.
Hemoglobin analysis is important for the diagnosis of alpha-thalassemia as it determines the types and percentages of types of hemoglobin present. Several different methods of hemoglobin analysis exist, including 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 ...
, capillary electrophoresis
Capillary electrophoresis (CE) is a family of electrokinetic separation methods performed in submillimeter diameter capillaries and in micro- and nanofluidic channels. Very often, CE refers to capillary zone electrophoresis (CZE), but other elect ...
and high-performance liquid chromatography
High-performance liquid chromatography (HPLC), formerly referred to as high-pressure liquid chromatography, is a technique in analytical chemistry used to separate, identify, and quantify each component in a mixture. It relies on pumps to pa ...
.
Molecular analysis of DNA sequences (DNA analysis
Genetic testing, also known as DNA testing, is used to identify changes in DNA sequence or chromosome structure. Genetic testing can also include measuring the results of genetic changes, such as RNA analysis as an output of gene expression, or ...
) can be used for the confirmation of a diagnosis of alpha-thalassemia, particularly for the detection of alpha-thalassemia carriers (deletions or mutations in only one or two alpha-globin genes).
Treatment
Treatment for alpha-thalassemia may include 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 m ...
to maintain hemoglobin at a level that reduces symptoms of anemia. The decision to initiate transfusions depends on the clinical severity of the disease. Splenectomy
A splenectomy is the surgical procedure that partially or completely removes the spleen. The spleen is an important organ in regard to immunological function due to its ability to efficiently destroy encapsulated bacteria. Therefore, removal o ...
is a possible treatment option to increase total hemoglobin levels in cases of worsening anemia due to an overactive or enlarged spleen, or when transfusion therapy is not possible. However, splenectomy is avoided when other options are available due to an increased risk of serious infections and thrombosis
Thrombosis (from Ancient Greek "clotting") is the formation of a blood clot inside a blood vessel, obstructing the flow of blood through the circulatory system. When a blood vessel (a vein or an artery) is injured, the body uses platelets (thr ...
.
Additionally, 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 ...
may be a problem that would require surgery. Secondary complications from febrile episode should be monitored, and most individuals live without any need for treatment.[update 2013] Additionally, 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 of a patient and to produ ...
should be considered as a treatment (and cure), which is best done in early age. Other options, such as gene therapy
Gene therapy is a medical field which focuses on the genetic modification of cells to produce a therapeutic effect or the treatment of disease by repairing or reconstructing defective genetic material. The first attempt at modifying human D ...
, are still being developed.
A study by Kreger et al combining a retrospective review of three cases of alpha thalassemia major and a literature review of 17 cases found that in utero transfusion can lead to favorable outcomes. Successful hematopoietic cell transplantation was eventually carried out in four patients.
Epidemiology
Worldwide distribution of inherited alpha-thalassemia corresponds to areas of malaria
Malaria is a mosquito-borne infectious disease that affects humans and other animals. Malaria causes symptoms that typically include fever, tiredness, vomiting, and headaches. In severe cases, it can cause jaundice, seizures, coma, or deat ...
exposure, suggesting a protective role. Thus, alpha-thalassemia is common in sub-Saharan Africa, the Mediterranean Basin
In biogeography, the Mediterranean Basin (; also known as the Mediterranean Region or sometimes Mediterranea) is the region of lands around the Mediterranean Sea that have mostly a Mediterranean climate, with mild to cool, rainy winters and w ...
, and generally tropical (and subtropical) regions. The epidemiology of alpha-thalassemia in the US reflects this global distribution pattern. More specifically, HbH disease is seen in Southeast Asia
Southeast Asia, also spelled South East Asia and South-East Asia, and also known as Southeastern Asia, South-eastern Asia or SEA, is the geographical United Nations geoscheme for Asia#South-eastern Asia, south-eastern region of Asia, consistin ...
and the Middle East
The Middle East ( ar, الشرق الأوسط, ISO 233: ) is a geopolitical region commonly encompassing Arabia (including the Arabian Peninsula and Bahrain), Asia Minor (Asian part of Turkey except Hatay Province), East Thrace (Europ ...
, while Hb Bart hydrops fetalis is acknowledged in Southeast Asia only.
The data indicate that 15% of the Greek
Greek may refer to:
Greece
Anything of, from, or related to Greece, a country in Southern Europe:
*Greeks, an ethnic group.
*Greek language, a branch of the Indo-European language family.
**Proto-Greek language, the assumed last common ancestor ...
and Turkish Cypriots
Turkish Cypriots or Cypriot Turks ( tr, Kıbrıs Türkleri or ''Kıbrıslı Türkler''; el, Τουρκοκύπριοι, Tourkokýprioi) are ethnic Turks originating from Cyprus. Following the Ottoman conquest of the island in 1571, about 30,0 ...
are carriers of beta-thalassaemia genes, while 10% of the population carry alpha-thalassaemia genes.[Haematology Made Easy. AuthorHouse. 2013-02-06. .page 246]
See also
* Beta-thalassemia
Beta thalassemias (β thalassemias) are a group of inherited blood disorders. They are forms of thalassemia caused by reduced or absent synthesis of the beta chains of hemoglobin that result in variable outcomes ranging from severe anemia to cl ...
* Delta-thalassemia
* Hemoglobinopathy
Hemoglobinopathy is the medical term for a group of inherited blood disorders and diseases that primarily affect red blood cells. They are single-gene disorders and, in most cases, they are inherited as autosomal co-dominant traits.
There are tw ...
References
Further reading
*
*
External links
*
{{DEFAULTSORT:Alpha-Thalassemia
Disorders of globin and globulin proteins
Hereditary hemolytic anemias