View source for Medicine:Beta thalassemia

{{short description|Thalassemia characterized by the reduced or absent synthesis of the beta globin chains of hemoglobin}}
{{Infobox medical condition (new)
| name            = Beta-thalassemia
| synonyms        = Microcytemia, beta type<ref name=genh/>
| image           = Thalassemia beta.jpg
|alt=
| caption         = Beta thalassemia genetics, the picture shows one example of how beta thalassemia is inherited. The beta globin gene is located on chromosome 11. A child inherits two beta globin genes (one from each parent).
| pronounce       =
| field           = [[Medicine:Hematology|Hematology]]
| symptoms        =
| complications   =
| onset           =
| duration        =
| types           = Thalassemia minor, intermediate and major<ref name=emedicine.medscape.com/>
| causes          = Mutations in the HBB gene<ref name=genh/>
| risks           =
| diagnosis       = DNA analysis<ref name=mat/>
| differential    =
| prevention      =
| treatment       = Depends on type (see types)
| medication      =
| prognosis       =
| frequency       =
| deaths          =
}}
'''Beta thalassemias''' ('''β thalassemias''') are a group of [[Medicine:Genetic disorder|inherited]] [[Medicine:Hemoglobinopathy|blood disorders]]. They are forms of [[Medicine:Thalassemia|thalassemia]] caused by reduced or absent synthesis of the [[Biology:HBB|beta chains]] of [[Biology:Hemoglobin|hemoglobin]] that result in variable outcomes ranging from severe [[Medicine:Anemia|anemia]] to clinically asymptomatic individuals. Global annual incidence is estimated at one in 100,000.<ref name=PMC2893117>{{Cite journal| last1 =Galanello  | first1 =Renzo  | last2 = Origa  | first2 =Raffaella  | title =Beta-thalassemia  | date =21 May 2010  | doi =  10.1186/1750-1172-5-11|pmc=2893117 | pmid=20492708 | volume=5 | page=11 | journal=Orphanet J Rare Dis | doi-access =free }}</ref> Beta thalassemias occur due to malfunctions in the hemoglobin subunit beta or HBB. The severity of the disease depends on the nature of the mutation.<ref>{{Cite book|title = Goldman-Cecil Medicine: Expert Consult - Online|url = https://books.google.com/books?id=40Z9CAAAQBAJ&q=beta+thalassemia++mutation+hbb+gene+caused&pg=RA7-PA93|publisher = Elsevier Health Sciences|date = 2015-04-21|isbn = 9780323322850|first1 = Lee|last1 = Goldman|first2 = Andrew I.|last2 = Schafer}}</ref>

HBB blockage over time leads to decreased beta-chain synthesis. The body's inability to construct new beta-chains leads to the underproduction of [[Biology:Hemoglobin A|HbA]] (adult hemoglobin).<ref>{{Cite book|title = Oxford Handbook of Clinical Pathology|url = https://books.google.com/books?id=XzZoAgAAQBAJ&q=beta+thalassemia+underproduction+of+HBA&pg=PA261|publisher = OUP Oxford|date = 2012-02-16|isbn = 9780191629938|first = James|last = Carton}}</ref> Reductions in HbA available overall to fill the red blood cells in turn leads to [[Medicine:Microcytic anemia|microcytic anemia]]. Microcytic anemia ultimately develops in respect to inadequate HBB protein for sufficient red blood cell functioning.<ref>{{Cite book|title = Pediatric Hospital Medicine: Textbook of Inpatient Management|url = https://books.google.com/books?id=sV6-ifUGoMYC&q=beta+thalassemia++microcytic+anemia&pg=PA337|publisher = Lippincott Williams & Wilkins|date = 2008|isbn = 9780781770323|first1 = Ronald M.|last1 = Perkin|first2 = Dale A.|last2 = Newton|first3 = James D.|last3 = Swift}}</ref> Due to this factor, the patient may require blood transfusions to make up for the blockage in the beta-chains. {{citation needed|date=September 2019}}
Repeated blood transfusions cause severe problems associated with iron overload.<ref>{{Cite journal|title = Beta-thalassemia|journal = Orphanet Journal of Rare Diseases|date = 2010-05-21|issn = 1750-1172|pmid = 20492708|pages = 11|volume = 5|issue = 1|doi = 10.1186/1750-1172-5-11|first1 = Renzo|last1 = Galanello|first2 = Raffaella|last2 = Origa|pmc=2893117 | doi-access=free }}</ref>

== Signs and symptoms ==
[[File:Anemia.JPG|thumb|The hand of a person with severe anemia (left, wearing ring) compared to one without]]

Three main forms have been described: thalassemia minor, thalassemia intermedia, and thalassemia major which vary from asymptomatic or mild symptoms to severe anemia requiring lifelong transfusions.<ref name="Taher">{{cite journal |last1=Taher |first1=Ali T. |last2=Musallam |first2=Khaled M. |last3=Cappellini |first3=M. Domenica |title=β-Thalassemias |journal=New England Journal of Medicine |date=25 February 2021 |volume=384 |issue=8 |pages=727–743 |doi=10.1056/NEJMra2021838|pmid=33626255 |s2cid=232049825 }}</ref> Individuals with beta thalassemia major (those who are homozygous for thalassemia mutations, or inheriting 2 mutations) usually present within the first two years of life with symptomatic severe anemia, poor growth, and skeletal abnormalities. Untreated thalassemia major eventually leads to death, usually by [[Medicine:Heart failure|heart failure]]; therefore, prenatal screening is very important.<ref>{{Cite book|title = Introduction to Pathology for the Physical Therapist Assistant|url = https://books.google.com/books?id=RTRv18iTn8YC&q=beta+thalassemia+major+symptoms&pg=PA170|publisher = Jones & Bartlett Publishers|date = 2011|isbn = 9780763799083}}</ref> Those with beta thalassemia intermedia (those who are [[Biology:Compound heterozygosity|compound heterozygotes]] for the beta thalassemia mutation) usually present later in life with mild to moderate symptoms of anemia.<ref name="Taher" /> Beta thalassemia trait (also known as beta thalassemia minor) involves heterozygous inheritance of a beta-thalassemia mutation and patients usually have borderline microcytic, hypochromic anemia and they are usually asymptomatic or have mild symptoms.<ref name="Taher" /> Beta thalassemia minor can also present as beta thalassemia silent carriers; those who inherit a beta thalassemic mutation but have no hematologic abnormalities nor symptoms.<ref name="Taher" /> Some people with thalassemia are susceptible to health complications that involve the [[Biology:Spleen|spleen]] (hypersplenism) and [[Medicine:Gallstone|gallstone]]s (due to hyperbilirubinemia from peripheral hemolysis).<ref name="Taher" /><ref name="genh">{{Cite web|title = Beta thalassemia|url = http://ghr.nlm.nih.gov/condition/beta-thalassemia|website = Genetics Home Reference|access-date = 2015-05-26}}</ref> These complications are mostly found in thalassemia major and intermedia patients.{{citation needed|date=December 2021}}

Excess iron (from [[Medicine:Hemolysis|hemolysis]] or transfusions) causes serious complications within the liver, heart, and endocrine glands. Severe symptoms include liver cirrhosis, liver fibrosis, and in extreme cases, [[Medicine:Liver cancer|liver cancer]].<ref>{{Cite book|title = Iron Physiology and Pathophysiology in Humans|url = https://books.google.com/books?id=wtmeZX2Ku6AC&q=beta+thalassemia+excess+iron&pg=PA329|publisher = Springer Science & Business Media|date = 2012-01-16|isbn = 9781603274845|first1 = Gregory J.|last1 = Anderson|first2 = Gordon D.|last2 = McLaren}}</ref> Heart failure, growth impairment, diabetes and osteoporosis are life-threatening conditions which can be caused by beta thalassemia major.<ref>{{Cite book|title = Handbook of Iron Overload Disorders|url = https://books.google.com/books?id=BUVBcNkAdrwC&q=beta+thalassemia+symptoms+and+signs+heart+failure+diabetes&pg=PA242|publisher = Cambridge University Press|date = 2010-07-22|isbn = 9781139489393|first1 = James C.|last1 = Barton|first2 = Corwin Q.|last2 = Edwards|first3 = Pradyumna D.|last3 = Phatak|first4 = Robert S.|last4 = Britton|first5 = Bruce R.|last5 = Bacon}}</ref> The main cardiac abnormalities seen as a result of beta thalassemia and iron overload include left ventricular systolic and diastolic dysfunction, pulmonary hypertension, valvulopathy, arrhythmias, and pericarditis. Increased gastrointestinal iron absorption is seen in all grades of beta thalassemia, and increased [[Biology:Red blood cell|red blood cell]] destruction by the spleen due to ineffective erythropoiesis further releases additional iron into the bloodstream.<ref>{{Cite book|title = Pathophysiology: The Biologic Basis for Disease in Adults and Children|url = https://books.google.com/books?id=3QgyAgAAQBAJ&q=beta+thalassemia+increased+red+blood+cell+destruction+by+the+spleen&pg=PA1070|publisher = Elsevier Health Sciences|date = 2013-12-13|isbn = 9780323088541|first1 = Kathryn L.|last1 = McCance|first2 = Sue E.|last2 = Huether}}</ref>

Additional symptoms of beta thalassemia major or intermedia include the classic symptoms of moderate to severe anemia including fatigue, growth and developmental delay in childhood, leg ulcers and organ failure.<ref name="Taher" /> Ineffective erythropoiesis (red blood cell production) can also lead to compensatory bone marrow expansion which can then lead to bony changes/deformities, bone pain and craniofacial abnormalities.<ref name="Taher" /> Extramedullary organs such as the liver and spleen that can also undergo erythropoiesis become activated leading to [[Medicine:Hepatosplenomegaly|hepatosplenomegaly]] (enlargement of the liver and spleen).<ref name="Taher" /> Other tissues in the body can also become sites of erythropoiesis, leading to extramedullary hematopoietic pseudotumors which may cause compressive symptoms if they occur in the thoracic cavity or spinal canal.<ref name="Taher" />

==Cause==

=== Mutations ===
Two major groups of mutations can be distinguished:
* Nondeletion forms: These defects, in general, involve a single base substitution or small insertions near or upstream of the β globin gene. Most often, mutations occur in the promoter regions preceding the beta-globin genes. Less often, abnormal splice variants are believed to contribute to the disease.<ref>{{Cite book|title = Molecular Pathology in Clinical Practice|url = https://books.google.com/books?id=Z2YNhh51SmQC&q=beta+thalassemia+nondeletion+form&pg=PA155|publisher = Springer Science & Business Media|date = 2007-11-25|isbn = 9780387332277|first = Debra G. B.|last = Leonard}}</ref>
* Deletion forms: Deletions of different sizes involving the β globin gene produce different syndromes such as (β<sup>o</sup>) or [[Medicine:Hereditary persistence of fetal hemoglobin|hereditary persistence of fetal hemoglobin]] syndromes.<ref>{{Cite book|title = Contemporary Internal Medicine: Clinical Case Studies|url = https://books.google.com/books?id=k-jiBwAAQBAJ&q=beta+thalassemia+deletion+form&pg=PA199|publisher = Springer Science & Business Media|date = 2012-12-06|isbn = 9781461567134|first1 = Juan M.|last1 = Bowen|first2 = Ernest L.|last2 = Mazzaferri}}</ref>
Mutations are characterized as (βo) if they prevent any formation of β globin chains, mutations are characterized as (β+) if they allow some β globin chain formation to occur.<ref name="Taher" />

{| class="wikitable"
|-
! Name
! Older synonyms
! Description
! Alleles
|-
| {{Visible anchor|Thalassemia minor}}
| &nbsp;
| [[Biology:Zygosity#Heterozygous|Heterozygous]] form: Only one of β globin alleles bears a mutation. Affected individuals will develop [[Medicine:Microcytic anemia|microcytic anemia]]. Detection usually involves lower than normal [[Medicine:Mean corpuscular volume|mean corpuscular volume]] value (<80&nbsp;fL).<ref>{{Cite book|title = NORD Guide to Rare Disorders|url = https://books.google.com/books?id=99YPDvFWBB0C&q=thalassemia+minor&pg=PA420|publisher = Lippincott Williams & Wilkins|date = 2003|isbn = 9780781730631|first = National Organization for Rare|last = Disorders}}</ref>
| β<sup>+</sup>/β<br>β<sup>o</sup>/β
|-
| {{Visible anchor|Thalassemia intermedia}}
| &nbsp;
| Affected individuals can often manage a normal life but may need occasional transfusions, e.g., at times of illness or pregnancy, depending on the severity of their anemia.<ref>{{Cite book|title = Hemochromatosis: Genetics, Pathophysiology, Diagnosis and Treatment|url = https://books.google.com/books?id=kE6mmwm5d8UC&q=thalassemia+intermedia&pg=PA437|publisher = Cambridge University Press|date = 2000-01-13|isbn = 9780521593809|first1 = James C.|last1 = Barton|first2 = Corwin Q.|last2 = Edwards}}</ref>
| β<sup>+</sup>/β<sup>+</sup><br>β<sup>o</sup>/β<sup>+</sup>
|-
| {{Visible anchor|Thalassemia major}}
| [[Place:Mediterranean Sea|Mediterranean]] anemia; Cooley anemia
| [[Biology:Zygosity#Homozygous|Homozygous form]]: Occurs when both alleles have thalassemia mutations. This is a severe microcytic, hypochromic anemia. Untreated, it causes anemia, splenomegaly and severe bone deformities, and progresses to death before age 20. Treatment consists of periodic [[Medicine:Blood transfusion|blood transfusion]]; [[Medicine:Splenectomy|splenectomy]] for splenomegaly and chelation of transfusion-related iron overload.<ref>{{Cite book|title = Professional Guide to Diseases|url = https://archive.org/details/isbn_9780781778992|url-access = registration|page = [https://archive.org/details/isbn_9780781778992/page/513 513]|quote = thalassemia major.|publisher = Lippincott Williams & Wilkins|date = 2009|isbn = 9780781778992|first = Lippincott Williams &|last = Wilkins}}</ref>
| β<sup>o</sup>/β<sup>o</sup>
|}

=== mRNA assembly ===
[[File:Protein HBB PDB 1a00.png|thumb|Protein HBB PDB 1a00. This is a healthy beta globin protein.]]

Beta thalassemia is a hereditary disease affecting hemoglobin. As with about half of all hereditary diseases,<ref name="Ward+Cooper2010">{{cite journal |doi=10.1002/path.2649 |title=The pathobiology of splicing |year=2009 |last1=Ward |first1=Amanda J |last2=Cooper |first2=Thomas A |journal=The Journal of Pathology |pmid=19918805 |pages=152–63 |volume=220 |issue=2 |pmc=2855871}}</ref> an inherited mutation damages the assembly of the [[Biology:Messenger RNA|messenger-type RNA]] (mRNA) that is transcribed from a [[Biology:Chromosome|chromosome]]. DNA contains both the instructions ([[Biology:Gene|gene]]s) for stringing [[Chemistry:Amino acid|amino acid]]s together into [[Biology:Protein|protein]]s, as well as stretches of DNA that play important roles in regulating produced protein levels.<ref>{{Cite web|title = the definition of dna|url = http://dictionary.reference.com/browse/DNA|website = Dictionary.com|access-date = 2015-05-26}}</ref>

In thalassemia, an additional, contiguous length or a discontinuous fragment of non-coding instructions is included in the mRNA. This happens because the mutation obliterates the boundary between the [[Biology:Intron|intron]]ic and [[Biology:Exon|exon]]ic portions of the DNA template.<ref>{{Cite book|title = Practical Management of Haemoglobinopathies|url = https://books.google.com/books?id=EKrzg_DoSFcC&q=beta+thalassemia+disrupts+regulatory+function+mRNA&pg=PA31|publisher = John Wiley & Sons|date = 2008-04-15|isbn = 9781405140201|first = Iheanyi|last = Okpala}}</ref> Because all the coding sections may still be present, normal hemoglobin may be produced and the added genetic material, if it produces pathology, instead disrupts regulatory functions enough to produce anemia. Hemoglobin’s normal alpha and beta subunits each have an iron-containing central portion (heme) that allows the protein chain of a subunit to fold around it. Normal adult hemoglobin contains 2 alpha and 2 beta subunits.<ref>{{Cite book|title = Textbook of Biochemistry for Dental Students|url = https://books.google.com/books?id=5k95F6EFCTUC&q=Normal+adult+hemoglobin+contains+2+alpha+and+2+beta+subunits.&pg=PA142|publisher = JP Medical Ltd|date = 2011-11-01|isbn = 9789350254882|first1 = D. M.|last1 = Vasudevan|first2 = S.|last2 = Sreekumari|first3 = Kannan|last3 = Vaidyanathan}}</ref> Thalassemias typically affect only the mRNAs for production of the beta chains (hence the name). Since the mutation may be a change in only a single base ([[Biology:Single-nucleotide polymorphism|single-nucleotide polymorphism]]), on-going efforts seek [[Biology:Gene therapy|gene therapies]] to make that single correction.<ref>{{Cite book|title = Avery's Diseases of the Newborn|url = https://books.google.com/books?id=UxELwb0iOt0C&q=beta+thalassemia+mRNA&pg=PA1201|publisher = Elsevier Health Sciences|date = 2005|isbn = 978-0721693477|first1 = H. William|last1 = Taeusch|first2 = Roberta A.|last2 = Ballard|first3 = Christine A.|last3 = Gleason|first4 = Mary Ellen|last4 = Avery}}</ref><ref>{{Cite book|title = Beta Thalassemia: New Insights for the Healthcare Professional: 2013 Edition: ScholarlyBrief|url = https://books.google.com/books?id=sEJRvo6mHEUC&q=beta+thalassemia+single+nucleotide+polymorphism&pg=PT40|publisher = ScholarlyEditions|date = 2013-07-22|isbn = 9781481663472}}</ref>

==Risk factors==
Family history and ancestry are factors that increase the risk of beta thalassemia. Depending on family history, if a person's parents or grandparents had beta thalassemia major or intermedia, there is a 75% (3 out of 4) probability (see inheritance chart at top of page) of the mutated gene being inherited by an offspring. Even if a child does not have beta thalassemia major or intermedia, they can still be a carrier, possibly resulting in future generations of their offspring having beta thalassemia.{{citation needed|date=January 2019}}

Another risk factor is ancestry. Beta thalassemia occurs most often in people of Italian, Greek, Middle Eastern, Southern Asian, and African ancestry.<ref>{{cite web|title=Risk Factors|url=http://www.mayoclinic.org/diseases-conditions/thalassemia/symptoms-causes/dxc-20261829|website=Mayo Clinic|access-date=4 April 2017}}</ref>

== Diagnosis ==
[[File:B-Thal.jpg|Peripheral blood smear from a person with beta thalassemia. The red blood cells vary greatly in shape and size and some look empty because of their low hemoglobin content (Giemsa stain).|right|thumb]]

Abdominal pain due to hypersplenism, splenic infarction and right-upper quadrant pain caused by gallstones are major clinical manifestations. However, diagnosing thalassemia from symptoms alone is inadequate. Physicians note these signs as associative due to this disease's complexity.<ref>{{Cite web|title = How Are Thalassemias Diagnosed? - NHLBI, NIH|url = https://www.nhlbi.nih.gov/health/health-topics/topics/thalassemia/diagnosis|website = www.nhlbi.nih.gov|access-date = 2015-05-26}}</ref> The following associative signs can attest to the severity of the [[Biology:Phenotype|phenotype]]: pallor, poor growth, inadequate food intake, splenomegaly, [[Medicine:Jaundice|jaundice]], maxillary hyperplasia, dental malocclusion, cholelithiasis, systolic ejection murmur in the presence of severe anemia and pathologic fractures. Based on symptoms, tests are ordered for a [[Medicine:Differential diagnosis|differential diagnosis]]. These tests include [[Medicine:Complete blood count|complete blood count]]; [[Medicine:Hemoglobin electrophoresis|hemoglobin electrophoresis]]; serum transferrin, [[Biology:Ferritin|ferritin]], [[Medicine:Total iron-binding capacity|total iron-binding capacity]]; urine [[Chemistry:Urobilin|urobilin]] and urobilogen; peripheral blood smear, which may show codocytes, or target cells;<ref>[https://www1.imperial.ac.uk/departmentofmedicine/divisions/experimentalmedicine/haematology/morphology/bain/images/slide21/ Target Cells], Imperial College of London Department of Medicine</ref> [[Medicine:Hematocrit|hematocrit]]; and serum bilirubin.<ref name=orkin>{{cite book |first1=Stuart H. |last1=Orkin |first2=David G. |last2=Nathan |first3=David |last3=Ginsburg |first4=A. Thomas |last4=Look |first5=David E. |last5=Fisher |first6=Samuel |last6=Lux |year=2009 |title=Nathan and Oski's Hematology of Infancy and Childhood |edition=7th |publisher=Saunders |location=Philadelphia |isbn=978-1-4160-3430-8}}{{page needed|date=May 2012}}</ref><ref>{{Cite web|title = What Are the Signs and Symptoms of Thalassemias? - NHLBI, NIH|url = https://www.nhlbi.nih.gov/health/health-topics/topics/thalassemia/signs|website = www.nhlbi.nih.gov|access-date = 2015-05-26}}</ref> The expected pattern on hemoglobin electrophoresis in people with beta-thalassemia is an increased level of [[Biology:Hemoglobin A2|hemoglobin&nbsp;A2]] and slightly increased hemoglobin&nbsp;F.{{citation needed|date=August 2018}} The diagnosis is confirmed with hemoglobin electrophoresis or high performance liquid chromatography.<ref name="Taher" />

Skeletal changes associated with expansion of the bone marrow:
* Chipmunk facies: bossing of the skull, prominent malar eminence, depression of the bridge of the nose, tendency to a mongoloid slant of the eye, and exposure of the upper teeth due to hypertrophy of the maxillae.<ref>{{cite journal|last1=Galanello|first1=Renzo|last2=Origa|first2=Raffaella|title=Beta-thalassemia|journal=Orphanet Journal of Rare Diseases|date=2010|volume=5|issue=1|pages=11|doi=10.1186/1750-1172-5-11|pmid=20492708|pmc=2893117 |doi-access=free }}</ref>
* Hair-on-end (or "crew cut") on skull X-ray: new bone formation due to the inner table. {{citation needed|date=May 2018}}

=== DNA analysis ===

All beta thalassemias may exhibit abnormal red blood cells; a family history is followed by DNA analysis.<ref name="mat">{{Cite book|title = Maternal-Child Nursing|url = https://books.google.com/books?id=kbrwAwAAQBAJ&q=beta+thalassemia++abnormal+red+blood+cells&pg=PA623|publisher = Elsevier Health Sciences|date = 2014-04-17|isbn = 9780323293778|first1 = Emily Slone|last1 = McKinney|first2 = Susan R.|last2 = James|first3 = Sharon Smith|last3 = Murray|first4 = Kristine|last4 = Nelson|first5 = Jean|last5 = Ashwill}}</ref> This test is used to investigate deletions and mutations in the alpha- and beta-globin-producing genes. Family studies can be done to evaluate carrier status and the types of mutations present in other family members. DNA testing is not routine, but can help diagnose thalassemia and determine carrier status. In most cases the treating physician uses a clinical prediagnosis assessing anemia symptoms: fatigue, breathlessness and poor exercise tolerance.<ref>{{Cite book|title = Diagnostic Molecular Pathology in Practice: A Case-Based Approach|url = https://books.google.com/books?id=PTTaSp7ZJ2AC&q=beta+thalassemia++dna++test&pg=PA16|publisher = Springer Science & Business Media|date = 2011-09-09|isbn = 9783642196775|first = Iris|last = Schrijver}}</ref> Further genetic analysis may include HPLC should routine electrophoresis prove difficult.<ref name=orkin/>

==Prevention==
Beta thalassemia is a hereditary disease allowing for a preventative treatment by carrier screening and prenatal diagnosis. It can be prevented if one parent has normal genes, giving rise to screenings that empower carriers to select partners with normal hemoglobin. A study aimed at detecting the genes that could give rise to offspring with sickle cell disease. Patients diagnosed with beta thalassemia have MCH ≤ 26&nbsp;pg and an RDW < 19. Of 10,148 patients, 1,739 patients had a hemoglobin phenotype and RDW consistent with beta thalassemia. After the narrowing of patients, the HbA2 levels were tested presenting 77 patients with beta thalassemia.<ref>{{cite journal |title=Carrier screening for Beta-thalassaemia: a review of international practice |journal=European Journal of Human Genetics|volume=18|issue=10|pages=1077–83|pmid=20571509|pmc=2987452|year=2010|last1=Cousens|first1=N. E.|last2=Gaff|first2=C. L.|last3=Metcalfe|first3=S. A.|last4=Delatycki|first4=M. B.|doi=10.1038/ejhg.2010.90}}</ref> This screening procedure proved insensitive in populations of West African ancestry because of the indicators has high prevalence of alpha thalassemia. Countries have programs distributing information about the reproductive risks associated with carriers of haemoglobinopathies. Thalassemia carrier screening programs have educational programs in schools, armed forces, and through mass media as well as providing counseling to carriers and carrier couples.<ref>{{cite web|title=Screening for the beta-thalassaemia trait: hazards among populations of West African Ancestry|url=https://www.google.com/search?q=Screening+for+the+beta-thalassaemia+trait:+hazards+among+populations+of+West+African+Ancestry|access-date=4 April 2017}}</ref> Screening has shown reduced incidence; by 1995 the prevalence in Italy reduced from 1:250 to 1:4000, and a 95% decrease in that region. The decrease in incidence has benefitted those affected with thalassemia, as the demand for blood has decreased, therefore improving the supply of treatment.{{citation needed|date=May 2018}}

==Treatment==

===Beta thalassemia major===
[[File:Spleen after spleenectomy.jpg|thumb|Surgically removed spleen of a thalassemic child. It is about 15 times larger than normal.]]

Affected children require regular lifelong [[Medicine:Blood transfusion|blood transfusion]]s. [[Biology:Hematopoietic stem cell transplantation|Bone marrow transplants]] can be curative for some children.<ref name=pmid19678601>{{cite journal |first1=Herbert L. |last1=Muncie |first2=James S. |last2=Campbell |title=Alpha and Beta Thalassemia |journal=American Family Physician |pmid=19678601 |url=http://www.aafp.org/link_out?pmid=19678601 |year=2009 |volume=80 |issue=4 |pages=339–44}}</ref> Patients receive frequent blood transfusions that lead to or potentiate iron overload.<ref>{{Cite book|title = Wintrobe's Clinical Hematology|url = https://books.google.com/books?id=NYCeAgAAQBAJ&q=beta+thalassemia+major++bone+marrow&pg=RA1-PA149|publisher = Lippincott Williams & Wilkins|date = 2013-08-29|isbn = 9781469846224|first1 = John P.|last1 = Greer|first2 = Daniel A.|last2 = Arber|first3 = Bertil|last3 = Glader|first4 = Alan F.|last4 = List|first5 = Robert T.|last5 = Means|first6 = Frixos|last6 = Paraskevas|first7 = George M.|last7 = Rodgers}}</ref> Iron chelation treatment is necessary to prevent damage to internal organs in cases of iron overload. Advances in iron chelation treatments allow patients with thalassemia major to live long lives with access to proper treatment. Popular chelators include [[Chemistry:Deferoxamine|deferoxamine]] and [[Chemistry:Deferiprone|deferiprone]].<ref>{{Cite book|title = Wintrobe's Clinical Hematology|url = https://books.google.com/books?id=NYCeAgAAQBAJ&q=beta+thalassemia+major++iron+chelation&pg=RA1-PA148|publisher = Lippincott Williams & Wilkins|date = 2013-08-29|isbn = 9781469846224|first1 = John P.|last1 = Greer|first2 = Daniel A.|last2 = Arber|first3 = Bertil|last3 = Glader|first4 = Alan F.|last4 = List|first5 = Robert T.|last5 = Means|first6 = Frixos|last6 = Paraskevas|first7 = George M.|last7 = Rodgers}}</ref><ref>{{Cite book|title = Hydroxamic Acids: Advances in Research and Application: 2011 Edition: ScholarlyPaper|url = https://books.google.com/books?id=RpoJHhy-00wC&q=beta+thalassemia+major++iron+chelation+deferoxamine&pg=PA2|publisher = ScholarlyEditions|date = 2012-01-09|isbn = 9781464952081}}</ref>

The oral chelator [[Chemistry:Deferasirox|deferasirox]] was approved for use in 2005 in some countries.<ref>{{Cite web|title = NCBI - WWW Error Blocked Diagnostic|url = https://pubchem.ncbi.nlm.nih.gov/compound/deferoxamine#section=Top|website = pubchem.ncbi.nlm.nih.gov|access-date = 2015-05-26}}</ref><ref>{{Cite web|title = Deferoxamine|url = http://livertox.nih.gov/Deferoxamine.htm|website = livertox.nih.gov|access-date = 2015-05-26}}</ref> Bone marrow transplantation is the only cure and is indicated for patients with severe thalassemia major. Transplantation can eliminate a patient's dependence on transfusions. Absent a matching donor, a [[Biology:Savior sibling|savior sibling]] can be conceived by [[Medicine:Preimplantation genetic diagnosis|preimplantation genetic diagnosis]] (PGD) to be free of the disease as well as to match the recipient's [[Biology:Human leukocyte antigen|human leukocyte antigen]] (HLA) type.<ref>{{Cite journal|title = HLA-matched sibling bone marrow transplantation for β-thalassemia major|journal = Blood|date = 2011|issn = 0006-4971|pmid = 21119108|pages = 1745–1750|volume = 117|issue = 5|doi = 10.1182/blood-2010-09-306829|first1 = Mitchell|last1 = Sabloff|first2 = Mammen|last2 = Chandy|first3 = Zhiwei|last3 = Wang|first4 = Brent R.|last4 = Logan|first5 = Ardeshir|last5 = Ghavamzadeh|first6 = Chi-Kong|last6 = Li|first7 = Syed Mohammad|last7 = Irfan|first8 = Christopher N.|last8 = Bredeson|first9 = Morton J.|last9 = Cowan|pmc=3056598}}</ref>

Serum [[Biology:Ferritin|ferritin]] (the storage form of iron) is routinely measured in those with beta thalassemia to determine the degree of iron overload; with increased ferritin levels directing the use of iron chelation therapy. The three iron chelators; subcutaneous deferoxamine, oral deferiprone and oral deferasirox can be used as monotherapy or in combination, they have all been shown to decrease serum/systemic iron levels, hepatic and cardiac iron levels as well as decreasing the risk of cardiac arrhythmia, heart failure and death.<ref name="Taher" /> Hepatic and myocardial MRI is also used to quantify the iron deposition in target organs, especially the heart and liver, to guide therapy.<ref name="Taher" />

Scientists at Weill Cornell Medical College have developed a gene therapy strategy that could feasibly treat both beta-thalassemia and sickle cell disease. The technology is based on delivery of a lentiviral vector carrying both the human β-globin gene and an ankyrin insulator to improve gene transcription and translation, and boost levels of β-globin production.<ref>{{Cite web|title = Gene Therapy Shows Promise for Treating Beta-Thalassemia and Sickle Cell Disease|url = http://www.genengnews.com/gen-news-highlights/gene-therapy-shows-promise-for-treating-beta-thalassemia-and-sickle-cell-disease/81246554/|access-date = 2015-10-15|date = 2012-03-28}}</ref>

On June 10, 2022, a U.S. federal advisory panel recommended that the FDA approve a gene therapy treatment for use with beta thalassemia.<ref>{{cite web |title=From debilitating illness to a 'normal' life, new gene therapy treatment promises to transform rare disease |website=USA Today |author=Karen Weintraub |date=14 Jun 2022 |url=https://www.usatoday.com/story/news/health/2022/06/14/new-gene-therapy-treatment-promises-transform-rare-blood-disorder/7537324001}}</ref> The manufacturer Bluebird bio charges $2.8 million in the United States for its one-time treatment [[Biology:Zynteglo|Zynteglo]] (betibeglogene autotemcel).<ref>{{Cite web |last=Myshko |first=Denise |date=2022-04-13 |title=ICER Draft Report Finds Beti-Cel is Cost-Effective for Blood Disorder |url=https://www.managedhealthcareexecutive.com/view/icer-draft-report-finds-beti-cel-is-cost-effective-for-blood-disorder |access-date=2023-08-04 |website=Managed Health}}</ref><ref>{{Cite web |last=Kansteiner |first=Fraiser |date=2022-08-17 |title=UPDATED: Bluebird bio's $2.8M gene therapy Zynteglo wins FDA backing. Will its US launch take flight? |url=https://www.fiercepharma.com/pharma/bluebirds-28m-gene-therapy-zynteglo-gets-fda-backing-beta-thalassemia |access-date=2023-01-25 |website=Fierce Pharma |language=en}}</ref>

Gene editing therapies aimed at increasing [[Biology:Fetal hemoglobin|fetal hemoglobin]] production in beta thalassemia as well as [[Medicine:Sickle cell disease|sickle cell anemia]] by inhibiting the [[Biology:BCL11A|BCL11A]] gene are also being explored.<ref>{{Cite journal |last=Zipkin |first=Mark |date=2019-12-06 |title=CRISPR's "magnificent moment" in the clinic |url=https://www.nature.com/articles/d41587-019-00035-2 |journal=Nature Biotechnology |language=en |doi=10.1038/d41587-019-00035-2 |pmid=33277639 |s2cid=213060203}}</ref><ref>{{Cite news |date=2022-02-20 |title=Sickle cell: 'The revolutionary gene-editing treatment that gave me new life' |language=en-GB |work=BBC News |url=https://www.bbc.com/news/health-60348497 |access-date=2023-03-27}}</ref>

====Surgical====
Patients with thalassemia major are more inclined to have a splenectomy. The use of splenectomies have been declining in recent years due to decreased prevalence of hypersplenism in adequately transfused patients. Splenectomy is also associated with increased risk of infections and increased morbidity due to vascular disease, as the spleen is involved in scavenging to rid the body of pathologic or abnormal red blood cells.<ref name="Taher" /> Patients with hypersplenism are more likely to have a lower amount of healthy blood cells in their body than normal and reveal symptoms of anemia. The different surgical techniques are the open and laparoscopic method.<ref name="emedicine.medscape.com">{{cite web|last1=Advani|first1=Pooja|title=Beta Thalassemia Treatment & Management|url=http://emedicine.medscape.com/article/206490-treatment|website=Medscape|access-date=4 April 2017}}</ref> The laparoscopic method requires longer operating time but a shorter recovery period with a smaller and less prominent surgical scar. If it is unnecessary to remove the entire spleen a partial splenectomy may occur; this method preserves some of the immune function while reducing the probability of hypersplenism. Those undergoing splenectomy should receive an appropriate pneumococcal vaccine at least one week (preferably three weeks) before the surgery.<ref>{{cite web|last1=Uranüs|first1=Selman|title=Splenectomy for hematological disorders|url=https://www.ncbi.nlm.nih.gov/books/NBK6913/|website=NCBI|access-date=4 April 2017}}</ref>

====Therapeutic====
Long-term transfusion therapy (in those with transfusion dependent beta thalassemia) is a treatment used to maintain hemoglobin levels at a target pre-transfusion hemoglobin level of 9–10.5&nbsp;g/dL (11–12&nbsp;g/dL in those with concomitant heart disease).<ref name="Taher" /> To ensure quality blood transfusions, the packed red blood cells should be leucoreduced. By having leucoreduced blood packets, the patient is at a lower risk to develop adverse reactions by contaminated white cells and preventing platelet alloimmunisation.<ref>{{cite web|last1=A|first1=Cohen|title=Blood Transfusion Therapy in β-Thalassaemia Major|url=https://www.ncbi.nlm.nih.gov/books/NBK173967/|website=NCBI|access-date=4 April 2017}}</ref> Patients with allergic transfusion reactions or unusual red cell antibodies must receive washed red cells or cryopreserved red cells. Washed red cells have been removed of plasma proteins that would have become a target of the patient's antibodies allowing the transfusion to be carried out safely. Cryopreserved red cells are used to maintain a supply of rare donor units for patients with unusual red cell antibodies or missing common red cell antigens. These regular transfusions promote normal growth, physical activities and suppress bone marrow hyperactivity.{{citation needed|date=December 2021}}

====Pharmaceutical====
During normal iron homeostasis the circulating iron is bound to transferrin. But with iron overload (such as with frequent blood transfusions), the ability for transferrin to bind iron is exceeded and non-transferrin bound iron accumulated. This unbound iron is toxic due to its high propensity to induce oxygen species and is responsible for cellular damage. The prevention of iron overload protects patients from morbidity and mortality. The primary aim is to bind to and remove iron from the body and a rate equal to the rate of transfusional iron input or greater than iron input.<ref>{{cite web|last1=Advani|first1=Pooja|title=Beta Thalassemia Medication|url=http://emedicine.medscape.com/article/206490-medication|website=Medscape|access-date=4 April 2017}}</ref> Iron chelation is a medical therapy that may prevent the complications of iron overload.<ref name="Taher" /> Every unit of transfused blood contains 200–250&nbsp;mg of iron and the body has no natural mechanism to remove excess iron. The excess iron can be removed by iron chelators (deferoxamine, deferiprone and deferasirox).<ref>{{cite journal |last1=Cappellini |first1=Maria Domenica |title=Exjade® (deferasirox, ICL670) in the treatment of chronic iron overload associated with blood transfusion |journal=Therapeutics and Clinical Risk Management |volume=3 |issue=2 |pages=291–299 |issn=1176-6336|pmc=1936310 |year=2007 |pmid=18360637 |doi=10.2147/tcrm.2007.3.2.291 |doi-access=free }}</ref>

[[Biology:Luspatercept|Luspatercept]] (ACE-536) is a recombinant fusion protein that is used as a treatment in adults with transfusion dependent beta thalassemia. It consists of a modified extra-cellular domain of [[Biology:ACVR2B|human activin receptor type IIB]] bound to the Fc portion of the human IgG1 antibody.<ref name="Taher" /> The molecule binds to select transforming growth factor beta superfamily ligands to block [[Biology:SMAD (protein)|SMAD2 and 3]] signaling, thus enhancing erythroid maturation.<ref name="Taher" /> The medication has been shown to reduce the transfusion burden by 33% in adults with transfusion dependent beta thalassemia as compared to placebo and was also associated with decreased ferritin levels (with no significant decreases in liver or cardiac iron levels).<ref name="Taher" />

[[Biology:Exagamglogene autotemcel|Exagamglogene autotemcel]] was approved for medical use in the United Kingdom in November 2023.<ref>{{cite press release | title=MHRA authorises world-first gene therapy that aims to cure sickle-cell disease and transfusion-dependent β-thalassemia | website=[[Organization:Medicines and Healthcare products Regulatory Agency|Medicines and Healthcare products Regulatory Agency]] (MHRA) | date=16 November 2023 | url=https://www.gov.uk/government/news/mhra-authorises-world-first-gene-therapy-that-aims-to-cure-sickle-cell-disease-and-transfusion-dependent-thalassemia | access-date=8 December 2023 | archive-date=25 November 2023 | archive-url=https://web.archive.org/web/20231125015409/https://www.gov.uk/government/news/mhra-authorises-world-first-gene-therapy-that-aims-to-cure-sickle-cell-disease-and-transfusion-dependent-thalassemia | url-status=live }}</ref><ref name="Vertex PR">{{cite press release | title=Vertex and CRISPR Therapeutics Announce Authorization of the First CRISPR/Cas9 Gene-Edited Therapy, Casgevy (exagamglogene autotemcel), by the United Kingdom MHRA for the Treatment of Sickle Cell Disease and Transfusion-Dependent Beta Thalassemia | publisher=Vertex Pharmaceuticals | via=Business Wire | date=16 November 2023 | url=https://www.businesswire.com/news/home/20231115290500/en/%C2%A0Vertex-and-CRISPR-Therapeutics-Announce-Authorization-of-the-First-CRISPRCas9-Gene-Edited-Therapy-CASGEVY%E2%84%A2-exagamglogene-autotemcel-by-the-United-Kingdom-MHRA-for-the-Treatment-of-Sickle-Cell-Disease-and-Transfusion-Dependent-Beta-Thalassemia | access-date=9 December 2023 | archive-date=22 November 2023 | archive-url=https://web.archive.org/web/20231122154102/https://www.businesswire.com/news/home/20231115290500/en/%C2%A0Vertex-and-CRISPR-Therapeutics-Announce-Authorization-of-the-First-CRISPRCas9-Gene-Edited-Therapy-CASGEVY%E2%84%A2-exagamglogene-autotemcel-by-the-United-Kingdom-MHRA-for-the-Treatment-of-Sickle-Cell-Disease-and-Transfusion-Dependent-Beta-Thalassemia | url-status=live }}</ref>

=== Beta thalassemia intermedia ===
Patients with beta thalassemia intermedia require no transfusions or may require episodic blood transfusions during certain circumstances (infection, pregnancy, surgery).<ref name="Taher" /> Patients with frequent transfusions may develop iron overload and require [[Unsolved:Chelation therapy|chelation therapy]].<ref>{{Cite book|title = The 5 Minute Pediatric Consult|url = https://books.google.com/books?id=v7pbSFfMHCoC&q=bone+marrow+intermedia+transfusions++chelation++therapy&pg=PA871|publisher = Lippincott Williams & Wilkins|date = 2012|isbn = 9781451116564|first = M. William|last = Schwartz}}</ref> Transmission is autosomal recessive; however, dominant [[Biology:Mutation|mutation]]s and compound heterozygotes have been reported. [[Biology:Genetic counseling|Genetic counseling]] is recommended and prenatal diagnosis may be offered.<ref>{{Cite book|title = Blood and Bone Marrow Pathology|url = https://books.google.com/books?id=0Kaa7xbFC1gC&q=bone+marrow+intermedia&pg=RA2-PT462|publisher = Elsevier Health Sciences|date = 2011-05-27|isbn = 978-0702045356|first1 = Anna|last1 = Porwit|first2 = Jeffrey|last2 = McCullough|first3 = Wendy N.|last3 = Erber}}</ref>

=== Beta thalassemia minor ===
Patients with beta thalassemia minor are usually asymptomatic and are often monitored without treatment.<ref name="Taher" /> Beta thalassemia minor may coexist with other conditions such as [[Medicine:Hepatitis B|chronic hepatitis&nbsp;B]], [[Medicine:Hepatitis C|chronic hepatitis&nbsp;C]], [[Medicine:Non-alcoholic fatty liver disease|non-alcoholic fatty liver disease]] and [[Medicine:Alcoholic liver disease|alcoholic liver disease]] that, when combined or co-existing, may cause a person to have iron overload of the liver and more severe liver disease.<ref>{{Cite book | title = Guidelines for the Management of Transfusion Dependent Thalassaemia | url = https://www.ncbi.nlm.nih.gov/books/NBK269382/ | edition = 3rd | chapter = Liver Disease | chapter-url = https://www.ncbi.nlm.nih.gov/books/NBK269366/ | year = 2014 | first1 = Pierre | last1 = Brissot | first2 = Maria Domenica | last2 = Cappellini | journal = Zhonghua Nei Ke Za Zhi | volume = 28 | issue = 10 | pages = 609–11, 637 | publisher = Thalassaemia International Federation | editor = Cappellini MD, Cohen A, Porter J, Taher A, Viprakasit V | pmid = 2561094 | isbn = 9789963717064 }}</ref>

== Epidemiology ==
The beta form of thalassemia is particularly prevalent among the Mediterranean peoples and this geographical association is responsible for its naming: ''thalassa'' (''θάλασσα'') is the [[Social:Greek language|Greek]] word for sea and ''haima'' (''αἷμα'') is the Greek word for blood.<ref>{{OEtymD|thalassemia}}</ref><ref>{{LSJ|qa/lassa|θάλασσα}}, {{LSJ|ai({{=}}ma|αἷμα|ref}}.</ref>{{Citation needed|date=July 2019}} In [[Earth:Europe|Europe]], the highest concentrations of the disease are found in Greece and the [[Place:Turkey|Turkish]] coastal regions. The major Mediterranean islands (except the Balearics) such as [[Place:Sicily|Sicily]], Sardinia, [[Place:Corsica|Corsica]], [[Place:Cyprus|Cyprus]], Malta and Crete are heavily affected in particular.<ref>{{Cite web|title = WHO {{!}} Global epidemiology of haemoglobin disorders and derived service indicators|url =https://www.who.int/bulletin/volumes/86/6/06-036673/en/|archive-url =https://web.archive.org/web/20111030203104/http://www.who.int/bulletin/volumes/86/6/06-036673/en/|url-status =dead|archive-date =October 30, 2011|website = www.who.int|access-date = 2015-05-26}}</ref><ref>{{Cite book|title = The MGH Review of Critical Care Medicine|url = https://books.google.com/books?id=TftPBAAAQBAJ&q=beta+thalassemia+epidemiology+greek+turkey&pg=PA135|publisher = Lippincott Williams & Wilkins|date = 2013-10-16|isbn = 9781451173680|first1 = Sheri|last1 = Berg|first2 = Edward A.|last2 = Bittner}}</ref> Other Mediterranean peoples, as well as those in the vicinity of the Mediterranean, also have high incidence rates, including people from [[Place:West Asia|West Asia]] and [[Place:North Africa|North Africa]]. The data indicate that 15% of the Greek and Turkish Cypriots are carriers of beta-thalassaemia genes, while 10% of the population carry [[Medicine:Alpha-thalassemia|alpha-thalassaemia]] genes.<ref>{{Cite book|title = Haematology Made Easy|url = https://books.google.com/books?id=UCDcZFUo0YIC&q=beta+thalassemia+epidemiology+greek+turkey+north+africa&pg=PA246|publisher = AuthorHouse|date = 2013-02-06|isbn = 9781477246511}}</ref>

=== Evolutionary adaptation ===
The thalassemia trait may confer a degree of protection against [[Medicine:Malaria|malaria]],<ref>{{Cite book|title = Basic Genetics: A Primer Covering Molecular Composition of Genetic Material, Gene Expression and Genetic Engineering, and Mutations and Human Genetic|url = https://books.google.com/books?id=5gMiqaiJ0VAC&q=The+thalassemia+trait+may+confer+a+degree+of+protection+against+malaria&pg=PA237|publisher = Universal-Publishers|date = 2013|isbn = 9781612331928|first1 = Ahmed|last1 = Abouelmagd|first2 = Hussein M.|last2 = Ageely}}</ref> which is or was prevalent in the regions where the trait is common, thus conferring a selective survival advantage on carriers (known as heterozygous advantage), thus perpetuating the mutation. In that respect, the various thalassemias resemble another genetic disorder affecting hemoglobin, sickle-cell disease.<ref>{{cite book|last=Weatherall |first=David J |title=The Thalassemias: Disorders of Globin Synthesis |editor1-last=Lichtman  |editor1-first=MA  |editor2-last=Kipps  |editor2-first=TJ  |editor3-last=Seligsohn  |editor3-first=U  |editor4-last=Kaushansky |editor4-first=K  |editor5-last=Prchal |editor5-first=JT |work=Williams Hematology |edition=8 |chapter-url=http://www.accessmedicine.com/content.aspx?aID=6123722|chapter=Chapter 47. The Thalassemias: Disorders of Globin Synthesis |publisher=The McGraw-Hill Companies |year=2010 }}</ref>

=== Incidence ===
The disorder is more prevalent in certain ethnicities and age groups. Beta thalassemia is most prevalent in the "thalassemia belt" which includes areas in Sub-Saharan Africa, the Mediterranean extending into the Middle East and Southeast Asia.<ref name="Taher" /> This geographical distribution is thought to be due to beta-thalassemia carrier state (beta thalassemia minor) conferring a resistance to malaria.<ref name="Taher" /> In the United States, thalassemia's prevalence is approximately 1 in 272,000 or 1,000 people. There have been 4,000 hospitalized cases in England in 2002 and 9,233 consultant episodes for thalassemia. Men accounted for 53% of hospital consultant episodes and women accounted for 47%. The mean patient age is 23, with only 1% of consultants being older than 75, and 69% being 15–59. It is estimated that 1.5% of the world's population are carriers and 40,000 affected infants are born with the disease annually.<ref name="Taher" /> Beta thalassemia major is usually fatal in infancy if blood transfusions are not initiated immediately.<ref name="Children's Hospital & Research Center at Oakland">{{cite web|title=Thalassemia: Genetic Blood Disorder Expected To Double In Next Few Decades|url=https://www.sciencedaily.com/releases/2005/06/050620003719.htm|website=ScienceDaily|access-date=4 April 2017}}</ref>

==See also==
* [[Medicine:Alpha-thalassemia|Alpha-thalassemia]]
* [[Medicine:Anisopoikilocytosis|Anisopoikilocytosis]] 
* Delta-thalassemia
* [[Medicine:Hemoglobinopathy|Hemoglobinopathy]]

== References ==
{{Reflist}}

== Further reading ==
* {{cite book |first1=Antonio |last1=Cao |first2=Renzo |last2=Galanello |year=2010 |chapter=Beta-Thalassemia |chapter-url=https://www.ncbi.nlm.nih.gov/books/NBK1426/ |pmid=20301599 |editor1-first=Roberta A |editor1-last=Pagon |editor2-first=Thomas D |editor2-last=Bird |editor3-first=Cynthia R |editor3-last=Dolan |editor4-first=Karen |editor4-last=Stephens |editor5-first=Margaret P |editor5-last=Adam |title=GeneReviews|title-link=GeneReviews |publisher=University of Washington, Seattle }}
* {{cite journal|last1=Bahal|first1=Raman|last2=McNeer|first2=Nicole Ali|last3=Quijano|first3=Elias|last4=Liu|first4=Yanfeng|last5=Sulkowski|first5=Parker|last6=Turchick|first6=Audrey|last7=Lu|first7=Yi-Chien|last8=Bhunia|first8=Dinesh C.|last9=Manna|first9=Arunava|last10=Greiner|first10=Dale L.|last11=Brehm|first11=Michael A.|last12=Cheng|first12=Christopher J.|last13=López-Giráldez|first13=Francesc|last14=Ricciardi|first14=Adele|last15=Beloor|first15=Jagadish|last16=Krause|first16=Diane S.|last17=Kumar|first17=Priti|last18=Gallagher|first18=Patrick G.|last19=Braddock|first19=Demetrios T.|last20=Saltzman|first20=W. Mark|last21=Ly|first21=Danith H.|last22=Glazer|first22=Peter M.|title=In vivo correction of anaemia in β-thalassemic mice by γPNA-mediated gene editing with nanoparticle delivery|journal=Nature Communications|date=26 October 2016|volume=7|pages=13304|doi=10.1038/ncomms13304|pmid=27782131|pmc=5095181|language=en|issn=2041-1723|bibcode=2016NatCo...713304B}}

== External links ==
{{Medical resources
| DiseasesDB      = 3087
| ICD10           = {{ICD10|D|56|1|d|55}}
| ICD9            = {{ICD9|282.44}}
| ICDO            =
| OMIM            = 141900
| MedlinePlus     =
| eMedicineSubj   = article
| eMedicineTopic  = 199534
| MeshID          = D017086
| Orphanet        = 848
}}
{{Diseases of RBCs}}

{{DEFAULTSORT:Beta-Thalassemia}}
[[Category:Disorders of globin and globulin proteins]]
[[Category:Rare diseases]]

{{Sourceattribution|Beta thalassemia}}