Alpha-thalassemia: Difference between revisions

Revision as of 12:35, 31 December 2024

Alpha-thalassemia

Alpha-thalassemia is a blood disorder that reduces the production of hemoglobin. Hemoglobin is the protein in red blood cells that carries oxygen to cells throughout the body. Alpha-thalassemia is caused by mutations in the HBA1 and HBA2 genes, which are responsible for the production of alpha-globin, a component of hemoglobin.

Pathophysiology

In alpha-thalassemia, the production of alpha-globin chains is reduced or absent. This leads to an imbalance in the ratio of alpha to beta-globin chains, resulting in the formation of abnormal hemoglobin molecules. The severity of the disease depends on the number of affected alpha-globin genes.

Genetic Basis

The HBA1 and HBA2 genes are located on chromosome 16. Each person has four alpha-globin genes, two from each parent. The severity of alpha-thalassemia is determined by the number of gene deletions:

Silent Carrier: One gene deletion, usually asymptomatic.
Alpha-thalassemia Trait: Two gene deletions, mild anemia.
Hemoglobin H Disease: Three gene deletions, moderate to severe anemia.
Hydrops Fetalis: Four gene deletions, usually fatal before or shortly after birth.

Clinical Features

The clinical presentation of alpha-thalassemia varies depending on the number of affected genes.

Silent Carrier

Individuals with one deleted alpha-globin gene are typically asymptomatic and have normal hematological parameters.

Alpha-thalassemia Trait

Individuals with two deleted alpha-globin genes may have mild anemia and microcytosis. They are often asymptomatic and may be identified during routine blood tests.

Hemoglobin H Disease

This condition results from the deletion of three alpha-globin genes. It is characterized by:

Moderate to severe anemia
Splenomegaly
Jaundice
Bone deformities

Hydrops Fetalis

This is the most severe form of alpha-thalassemia, resulting from the deletion of all four alpha-globin genes. It leads to:

Severe anemia
Heart failure
Edema
Usually results in stillbirth or death shortly after birth

Diagnosis

Diagnosis of alpha-thalassemia involves:

Complete blood count (CBC) showing microcytic anemia
Hemoglobin electrophoresis
Genetic testing to identify deletions in the HBA1 and HBA2 genes

Management

Management of alpha-thalassemia depends on the severity of the disease:

Silent Carrier and Alpha-thalassemia Trait: Usually require no treatment.
Hemoglobin H Disease: May require regular blood transfusions, folic acid supplementation, and splenectomy in severe cases.
Hydrops Fetalis: Prenatal diagnosis and counseling are important. Intrauterine transfusions may be considered.

Prognosis

The prognosis of alpha-thalassemia varies:

Silent carriers and individuals with alpha-thalassemia trait generally have a normal life expectancy.
Hemoglobin H disease can lead to complications but is manageable with treatment.
Hydrops fetalis is usually fatal without intervention.

Prevention

Genetic counseling is recommended for at-risk couples. Prenatal testing can identify affected fetuses, allowing for informed decision-making.

@@ Line 1: / Line 1: @@
-== Alpha-thalassemia ==
+Alpha-thalassemia
-{{short description|Thalassemia involving the genes HBA1and HBA2 hemoglobin genes}}
+Alpha-thalassemia is a blood disorder that reduces the production of hemoglobin. Hemoglobin is the protein in red blood cells that carries oxygen to cells throughout the body. Alpha-thalassemia is caused by mutations in the HBA1 and HBA2 genes, which are responsible for the production of alpha-globin, a component of hemoglobin.
-{{Infobox medical condition (new)
-| name            = Alpha-thalassemia
-| synonyms        = α-thalassaemia
-| image           = Thalassemia alpha.jpg
-| caption         = Alpha-thalassemia inheritance pattern
-| pronounce       =
-| field           =
-| symptoms        = Jaundice, Fatigue<ref name=gene/>
-| complications   =
-| onset           =
-| duration        =
-| types           =
-| causes          = Deletions of chromosome 16p.<ref name=lip/>
-| risks           =
-| diagnosis       =  Haemoglobin electrophoresis<ref name=emed/>
-| differential    =
-| prevention      =
-| treatment       = Blood transfusion, possible splenectomy<ref name=gene/><ref name=com/>
-| medication      =
-| prognosis       =
-| frequency       =
-| deaths          =
-}}
-[[File:Alpha thalassemia chromosomes - Tamil.svg|thumb|Alpha_thalassemia_chromosomes_-_Tamil]]
+==Pathophysiology==
+In alpha-thalassemia, the production of alpha-globin chains is reduced or absent. This leads to an imbalance in the ratio of alpha to beta-globin chains, resulting in the formation of abnormal hemoglobin molecules. The severity of the disease depends on the number of affected alpha-globin genes.
+===Genetic Basis===
+The HBA1 and HBA2 genes are located on chromosome 16. Each person has four alpha-globin genes, two from each parent. The severity of alpha-thalassemia is determined by the number of gene deletions:
+* '''Silent Carrier''': One gene deletion, usually asymptomatic.
+* '''Alpha-thalassemia Trait''': Two gene deletions, mild anemia.
+* '''Hemoglobin H Disease''': Three gene deletions, moderate to severe anemia.
+* '''Hydrops Fetalis''': Four gene deletions, usually fatal before or shortly after birth.
+==Clinical Features==
-'''Alpha-thalassemia''' ('''α-thalassemia''', '''α-thalassaemia''') is a form of [[thalassemia]] involving the genes ''[[HBA1]]'' and ''[[HBA2]]''. Thalassemias are a group of [[Genetic disorder|inherited]] [[Blood diseases|blood conditions]] which result in the impaired production of [[hemoglobin]], the molecule that carries oxygen in the blood. Normal hemoglobin consists of two [[Alpha chain|alpha chains]] and two [[HBB|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]] destruction. The degree of impairment is based on which clinical [[phenotype]] is present (how many genes are affected).
+The clinical presentation of alpha-thalassemia varies depending on the number of affected genes.
-==Signs and symptoms==
+===Silent Carrier===
-The presentation of individuals with alpha-thalassemia consists of:
+Individuals with one deleted alpha-globin gene are typically asymptomatic and have normal hematological parameters.
-{| class="wikitable"
+===Alpha-thalassemia Trait===
-|+Signs and symptoms of alpha-thalassemia
-!Common
-!Uncommon
-|-
-|
-*[[Anemia]]: People with alpha-thalassemia can experience both a decrease in the production of red blood cells (RBC) and an increase in the destruction of RBCs which can result in other symptoms such as fatigue and dizziness.
-*[[Splenomegaly|Enlarged spleen]]
-*[[Gallstone|Gallstones]]
-*Delayed growth
-|
-*[[Jaundice]]
-*[[Skull bossing|Pronounced forehead]]: This occurs due to the expansion of the bone marrow in the frontal bone in the skull.The bone marrow expands because more blood cells are being produced in order to compensate for the [[anemia]].
-*[[Extramedullary hematopoiesis|Extramedullary hematopoesis]] (blood formation outside of the bone marrow)
-*[[Gestational hypertension|Hypertension (in pregnancy)]]
-|}
-<youtube>
+Individuals with two deleted alpha-globin genes may have mild anemia and microcytosis. They are often asymptomatic and may be identified during routine blood tests.
-title='''{{PAGENAME}}'''
-movie_url=http://www.youtube.com/v/R-POSKAhBL0
-&rel=1
-embed_source_url=http://www.youtube.com/v/R-POSKAhBL0
-&rel=1
-wrap = yes
-width=750
-height=600
-</youtube>
-==Cause==
+===Hemoglobin H Disease===
-Alpha-thalassemias are most commonly inherited in a [[Mendelian]] [[recessive]] manner. They are also associated with deletions of [[chromosome 16]]p.Alpha thalassemia can also be acquired under rare circumstances.
-==Pathophysiology==
+This condition results from the deletion of three alpha-globin genes. It is characterized by:
-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 chain]]s. The excess γ chains form tetramers which are poor carriers of O<sub>2</sub> since their affinity for O<sub>2</sub> is too high, so it is not dissociated in the periphery. [[Homozygote]] α<sup>0</sup> thalassaemias, where numerous γ<sub>4</sub> but no α-globins occur at all (referred to as [[Hemoglobin Barts|Hb Barts]]), often result in death soon after birth.
+* Moderate to severe anemia
+* Splenomegaly
+* Jaundice
+* Bone deformities
-==Diagnosis==
+===Hydrops Fetalis===
-Diagnosis of alpha-thalassemia is primarily by laboratory evaluation and [[molecular diagnosis]]. Alpha-thalassemia can be mistaken for [[Iron-deficiency anemia|iron-deficiency anaemia]] on a full blood count or blood film, as both conditions have a microcytic anaemia. [[Serum iron]] and [[serum ferritin]] can be used to exclude iron-deficiency [[anaemia]].
-===Types===
+This is the most severe form of alpha-thalassemia, resulting from the deletion of all four alpha-globin genes. It leads to:
-Two genetic [[loci]] exist for [[α globin]], thus four alleles are in [[Diploid cell|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.
-{| class="wikitable"
+* Severe anemia
-|-
+* Heart failure
-!Alleles affected
+* Edema
-!Description
+* Usually results in stillbirth or death shortly after birth
-!Genotype
-|-
-|''One''
-|This is known as '''alpha thalassemia silent''' and with this type, the effect on hemoglobin synthesis is minimal. Three α-globin genes are enough to permit normal hemoglobin production, and no clinical symptoms present. It occurs due to a deletion or non-deletion mutation.<ref name="gene">{{cite journal|last1=Origa|first1=Raffaella|last2=Moi|first2=Paolo|last3=Galanello|first3=Renzo|last4=Cao|first4=Antonio|title=Alpha-Thalassemia|journal=GeneReviews|date=1 January 1993|url=https://www.ncbi.nlm.nih.gov/books/NBK1435/|access-date=22 September 2016}}update 2013</ref>
-| - α/α α
-|-
-|''Two''
-|[[Image:Illu blood cell lineage.jpg|thumb|right|200px|Haematopoiesis(production of blood cells)]]
-The condition is called alpha thalassemia trait; two α genes permit nearly normal [[erythropoiesis|production of red blood cells]], but a mild [[microcytic anemia|microcytic]] [[hypochromic]] [[anemia]] is seen. The disease in this form can be mistaken for [[iron-deficiency anemia]] and treated inappropriately with iron.<ref name="emed">{{Cite web|url=http://emedicine.medscape.com/article/955496-workup|title=Alpha Thalassemia Workup: Approach Considerations, Laboratory Studies, Hemoglobin Electrophoresis|website=emedicine.medscape.com|access-date=2016-05-24}}</ref><ref name="gene" />
-Alpha-thalassemia trait can exist in two forms:
+==Diagnosis==
-*Alpha-thal-1 (- -/α α), involves ''cis'' deletion of both alpha genes on the same chromosome. Higher incidence in people of Asian descent when compared with the general population.
+Diagnosis of alpha-thalassemia involves:
-*Alpha-thal-2 (- α/- α), involves ''trans'' deletion of alpha genes; this occurs on different (homologous) chromosomes. Higher incidence in people of African descent when compared with the general population.
-| - -/α α<br /> or<br />- α/- α
-|-
-|''Three''
-|This condition is called [[hemoglobin H disease]]; two unstable hemoglobins are present in the blood; [[hemoglobin Barts]] (tetrameric [[γ chain]]s) and hemoglobin H (tetrameric [[β chain]]s). Both of these unstable hemoglobins have a higher affinity for oxygen than normal hemoglobin.A microcytic hypochromic anemia with [[Target cell (codocyte)|target cell]]s and [[Heinz body|Heinz bodies]] (precipitated HbH) on the [[peripheral blood smear]] can occur, as well as [[hepatosplenomegaly]].  The disease is noticed in childhood or in early adult life; anemia and hepatosplenomegaly are noted.{{medical citation needed|date=September 2016}}
-| - -/- α
-|-
-|''Four''
-|This is known as alpha thalassemia major; these fetuses are [[oedema|edematous]], have little circulating hemoglobin, and the hemoglobin that is present is all tetrameric γ chains. When all four alleles are affected, the [[fetus]] likely will not survive gestation without ''in utero'' intervention; most infants with alpha-thalassemia major are stillborn with [[hydrops fetalis]]. Fetuses treated with [[intrauterine]] [[transfusions]] throughout pregnancy starting at an early gestational age can survive to birth with acceptable morbidity. After birth, the treatment options include bone marrow transplantation or continued chronic transfusions.
-| - -/- -
-|-
-| colspan="8" align="left" |α α/α α = normal: 'α α' before the '/' represents one chromosome, and 'α α' after the '/', its [[homologous chromosome]].
-|}
-===Laboratory Diagnosis===
+* Complete blood count (CBC) showing microcytic anemia
-* Initial laboratory diagnosis should include a [[complete blood count]] and [[red blood cell indices]]. As well, a [[peripheral blood smear]] should be carefully reviewed.
+* Hemoglobin electrophoresis
+* Genetic testing to identify deletions in the HBA1 and HBA2 genes
-* 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]], [[capillary electrophoresis]] and [[high-performance liquid chromatography]].
+==Management==
-* Molecular analysis of DNA sequences ([[Genetic testing|DNA analysis]]) 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 [[Hemoglobin, alpha 1|alpha-globin]] genes).
+Management of alpha-thalassemia depends on the severity of the disease:
-==Treatment==
+* '''Silent Carrier and Alpha-thalassemia Trait''': Usually require no treatment.
+* '''Hemoglobin H Disease''': May require regular blood transfusions, folic acid supplementation, and splenectomy in severe cases.
+* '''Hydrops Fetalis''': Prenatal diagnosis and counseling are important. Intrauterine transfusions may be considered.
-Treatment for alpha-thalassemia may include [[blood transfusions]] 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 (Spleen removal)|Splenectomy]] 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 (Spleen removal)|splenectomy]] is avoided when other options are available due to an increased risk of serious infections and [[thrombosis]].
+==Prognosis==
-Additionally, [[gallstones]] 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.
+The prognosis of alpha-thalassemia varies:
-Additionally, [[stem cell transplantation]] should be considered as a treatment (and cure), which is best done in early age. Other options, such as [[gene therapy]], are still being developed.
+* Silent carriers and individuals with alpha-thalassemia trait generally have a normal life expectancy.
+* Hemoglobin H disease can lead to complications but is manageable with treatment.
+* Hydrops fetalis is usually fatal without intervention.
-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.
+==Prevention==
-==Epidemiology==
+Genetic counseling is recommended for at-risk couples. Prenatal testing can identify affected fetuses, allowing for informed decision-making.
-[[File:Malaria.jpg|100 px|thumb|Malaria]]
-Worldwide distribution of [[inherited]] alpha-thalassemia corresponds to areas of [[malaria]] exposure, suggesting a protective role. Thus, alpha-thalassemia is common in sub-Saharan [[Africa]], the [[Mediterranean Basin]], 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]] and the [[Middle East]], while Hb Bart hydrops fetalis is acknowledged in Southeast Asia only.The data indicate that 15% of the [[Greek Cypriots|Greek]] and [[Turkish Cypriots]] are carriers of [[beta-thalassaemia]] genes, while 10% of the population carry alpha-thalassaemia genes.
-==See also==
+==See Also==
-*[[Beta-thalassemia]]
+* [[Thalassemia]]
-*[[Delta-thalassemia]]
+* [[Hemoglobinopathy]]
-*[[Hemoglobinopathy]]
+* [[Anemia]]
-{{Diseases of RBCs}}
+{{Thalassemia}}
-{{DEFAULTSORT:Alpha-Thalassemia}}
-[[Category:Disorders of globin and globulin proteins]]
-[[Category:Hereditary hemolytic anemias]]
-{{rarediseases}}
+[[Category:Genetic disorders]]
-<references />
+[[Category:Hematology]]
+[[Category:Blood disorders]]