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beta Thalassemia(BTHAL)

MedGen UID:
2611
Concept ID:
C0005283
Disease or Syndrome
Synonyms: BTHAL; Cooley's anemia; Erythroblastic anemia; Mediterranean anemia
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
Concept ID:
C0441748
Intellectual Product
Sources: HPO, OMIM, Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in individuals with two pathogenic alleles, either homozygotes (two copies of the same mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele).
Autosomal dominant inheritance
MedGen UID:
141047
Concept ID:
C0443147
Intellectual Product
Sources: HPO, OMIM, Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in heterozygotes. In the context of medical genetics, an autosomal dominant disorder is caused when a single copy of the mutant allele is present. Males and females are affected equally, and can both transmit the disorder with a risk of 50% for each child of inheriting the mutant allele.
Autosomal recessive inheritance (HPO, OMIM, Orphanet)
Autosomal dominant inheritance (HPO, OMIM, Orphanet)
SNOMED CT: beta Thalassemia (65959000); Beta thalassemia (65959000); Beta thalassemia syndrome (65959000)
 
Genes (locations): HBB (11p15.4); HBB-LCR (11p15.4)
OMIM®: 613985
Orphanet: ORPHA848

Disease characteristics

Excerpted from the GeneReview: Beta-Thalassemia
Beta-thalassemia (β-thalassemia) is characterized by reduced synthesis of the hemoglobin subunit beta (hemoglobin beta chain) that results in microcytic hypochromic anemia, an abnormal peripheral blood smear with nucleated red blood cells, and reduced amounts of hemoglobin A (HbA) on hemoglobin analysis. Individuals with thalassemia major have severe anemia and hepatosplenomegaly; they usually come to medical attention within the first two years of life. Without treatment, affected children have severe failure to thrive and shortened life expectancy. Treatment with a regular transfusion program and chelation therapy, aimed at reducing transfusion iron overload, allows for normal growth and development and may improve the overall prognosis. Individuals with thalassemia intermedia present later and have milder anemia that does not require regular treatment with blood transfusion. These individuals are at risk for iron overload secondary to increased intestinal absorption of iron as a result of ineffective erythropoiesis. [from GeneReviews]
Authors:
Raffaella Origa   view full author information

Additional descriptions

From OMIM
Beta-thalassemia is characterized by a reduced production of hemoglobin A (HbA, alpha-2/beta-2), which results from the reduced synthesis of beta-globin chains relative to alpha-globin chains, thus causing an imbalance in globin chain production and hence abnormal erythropoiesis. The disorder is clinically heterogeneous (summary by Ottolenghi et al., 1975). Absence of beta globin causes beta-zero-thalassemia. Reduced amounts of detectable beta globin causes beta-plus-thalassemia. For clinical purposes, beta-thalassemia is divided into thalassemia major (transfusion dependent), thalassemia intermedia (of intermediate severity), and thalassemia minor (asymptomatic, carrier state). The molecular and clinical aspects of the beta-thalassemias were reviewed by Olivieri (1999). The remarkable phenotypic diversity of the beta-thalassemias reflects the heterogeneity of mutations at the HBB locus, the action of many secondary and tertiary modifiers, and a wide range of environmental factors (Weatherall, 2001).  http://www.omim.org/entry/613985
From GHR
Beta thalassemia is a blood disorder that reduces the production of hemoglobin. Hemoglobin is the iron-containing protein in red blood cells that carries oxygen to cells throughout the body.In people with beta thalassemia, low levels of hemoglobin lead to a lack of oxygen in many parts of the body. Affected individuals also have a shortage of red blood cells (anemia), which can cause pale skin, weakness, fatigue, and more serious complications. People with beta thalassemia are at an increased risk of developing abnormal blood clots.Beta thalassemia is classified into two types depending on the severity of symptoms: thalassemia major (also known as Cooley's anemia) and thalassemia intermedia. Of the two types, thalassemia major is more severe.The signs and symptoms of thalassemia major appear within the first 2 years of life. Children develop life-threatening anemia. They do not gain weight and grow at the expected rate (failure to thrive) and may develop yellowing of the skin and whites of the eyes (jaundice). Affected individuals may have an enlarged spleen, liver, and heart, and their bones may be misshapen. Some adolescents with thalassemia major experience delayed puberty. Many people with thalassemia major have such severe symptoms that they need frequent blood transfusions to replenish their red blood cell supply. Over time, an influx of iron-containing hemoglobin from chronic blood transfusions can lead to a buildup of iron in the body, resulting in liver, heart, and hormone problems.Thalassemia intermedia is milder than thalassemia major. The signs and symptoms of thalassemia intermedia appear in early childhood or later in life. Affected individuals have mild to moderate anemia and may also have slow growth and bone abnormalities.  https://ghr.nlm.nih.gov/condition/beta-thalassemia

Clinical features

Cholelithiasis
MedGen UID:
3039
Concept ID:
C0008350
Disease or Syndrome
Hard, pebble-like deposits that form within the gallbladder.
Jaundice
MedGen UID:
43987
Concept ID:
C0022346
Sign or Symptom
A clinical manifestation of HYPERBILIRUBINEMIA, characterized by the yellowish staining of the SKIN; MUCOUS MEMBRANE; and SCLERA. Clinical jaundice usually is a sign of LIVER dysfunction.
Splenomegaly
MedGen UID:
52469
Concept ID:
C0038002
Finding
Abnormal enlargement of the spleen.
Polycythemia
MedGen UID:
18552
Concept ID:
C0032461
Disease or Syndrome
Abnormally high mass or concentration of red blood cells in the blood, either due to an increase in erythropoiesis or a decrease in plasma volume.
Microcytic anemia
MedGen UID:
39081
Concept ID:
C0085576
Disease or Syndrome
Finberg et al. (2008) referred to this phenotype as iron-refractory iron deficiency anemia (IRIDA) and reviewed the key features: a congenital hypochromic, microcytic anemia; a very low mean corpuscular erythrocyte volume; a low transferrin saturation; abnormal iron absorption characterized by no hematologic improvement following treatment with oral iron; and abnormal iron utilization characterized by a sluggish, incomplete response to parenteral iron. The authors noted that although urinary levels of hepcidin (606464) are typically undetectable in individuals with iron deficiency, in 5 individuals with IRIDA urinary hepcidin/creatinine ratios were within or above the normal range.
Decreased mean corpuscular volume
MedGen UID:
65135
Concept ID:
C0221265
Finding
Persistence of hemoglobin F
MedGen UID:
68693
Concept ID:
C0239941
Finding
A laboratory test result indicating an abnormal amount of fetal hemoglobin in a biological sample.
Hypochromic microcytic anemia
MedGen UID:
124413
Concept ID:
C0271901
Disease or Syndrome
A type of anemia characterized by an abnormally low concentration of hemoglobin in the erythrocytes and lower than normal size of the erythrocytes.
Heinz body anemia
MedGen UID:
148583
Concept ID:
C0700299
Disease or Syndrome
This is a form of nonspherocytic hemolytic anemia of Dacie type I (in vitro autohemolysis is not corrected by added glucose). After splenectomy, which has little benefit, basophilic inclusions called Heinz bodies are demonstrable in the erythrocytes. Before splenectomy, diffuse or punctate basophilia may be evident. Most of these cases are probably instances of hemoglobinopathy. The hemoglobin demonstrates heat lability. Heinz bodies are observed also with the Ivemark syndrome (asplenia with cardiovascular anomalies; 208530).
Diamond-Blackfan anemia
MedGen UID:
266045
Concept ID:
C1260899
Disease or Syndrome
Diamond-Blackfan anemia (DBA) in its classic form is characterized by a profound normochromic and usually macrocytic anemia with normal leukocytes and platelets, congenital malformations in up to 50% of affected individuals, and growth retardation in 30% of affected individuals. The hematologic complications occur in 90% of affected individuals during the first year of life. The phenotypic spectrum ranges from a mild form (e.g., mild anemia, no anemia with only subtle erythroid abnormalities, physical malformations without anemia) to a severe form of fetal anemia resulting in nonimmune hydrops fetalis. DBA is associated with an increased risk for acute myelogenous leukemia (AML), myelodysplastic syndrome (MDS), and solid tumors including osteogenic sarcoma.
Reduced beta/alpha synthesis ratio
MedGen UID:
868732
Concept ID:
C4023137
Finding
A reduction in the ratio of production of beta globin to that of alpha globin. This is the major abnormality in the various forms of beta thalassemia.
Increased red cell sickling tendency
MedGen UID:
870257
Concept ID:
C4024695
Finding
Macrocytic hemolytic disease
MedGen UID:
870731
Concept ID:
C4025185
Disease or Syndrome
Cyanosis
MedGen UID:
1189
Concept ID:
C0010520
Sign or Symptom
A bluish or purplish discoloration of the skin and mucous membranes due to an increase in the amount of deoxygenated hemoglobin in the blood or a structural defect in the hemoglobin molecule.
Hematuria
MedGen UID:
5488
Concept ID:
C0018965
Disease or Syndrome
Blood in the urine.
Priapism
MedGen UID:
19462
Concept ID:
C0033117
Disease or Syndrome
A painful and harmful medical condition in which the erect penis doesn't return to its flaccid state, despite the absence of both physical and psychological stimulation, within four hours.
Impaired renal concentrating ability
MedGen UID:
395351
Concept ID:
C1859819
Finding
A defect in the ability to concentrate the urine.
Osteomyelitis
MedGen UID:
10497
Concept ID:
C0029443
Disease or Syndrome
An acute or chronic inflammation of the bone and its structures due to infection with pyogenic bacteria.
Splenomegaly
MedGen UID:
52469
Concept ID:
C0038002
Finding
Abnormal enlargement of the spleen.
Hematuria
MedGen UID:
5488
Concept ID:
C0018965
Disease or Syndrome
Blood in the urine.
Osteomyelitis
MedGen UID:
10497
Concept ID:
C0029443
Disease or Syndrome
An acute or chronic inflammation of the bone and its structures due to infection with pyogenic bacteria.
Aseptic necrosis
MedGen UID:
892371
Concept ID:
C2110211
Finding
Cyanosis
MedGen UID:
1189
Concept ID:
C0010520
Sign or Symptom
A bluish or purplish discoloration of the skin and mucous membranes due to an increase in the amount of deoxygenated hemoglobin in the blood or a structural defect in the hemoglobin molecule.
Jaundice
MedGen UID:
43987
Concept ID:
C0022346
Sign or Symptom
A clinical manifestation of HYPERBILIRUBINEMIA, characterized by the yellowish staining of the SKIN; MUCOUS MEMBRANE; and SCLERA. Clinical jaundice usually is a sign of LIVER dysfunction.

Recent clinical studies

Etiology

Klaihmon P, Lertthammakiat S, Anurathapan U, Pakakasama S, Sirachainan N, Hongeng S, Pattanapanyasat K
Thromb Res 2018 Sep;169:8-14. Epub 2018 Jul 4 doi: 10.1016/j.thromres.2018.07.007. PMID: 29990620
Graffeo L, Vitrano A, Scondotto S, Dardanoni G, Pollina Addario WS, Giambona A, Sacco M, Di Maggio R, Renda D, Taormina F, Triveri A, Attanasio M, Gluud C, Maggio A
Eur J Intern Med 2018 Aug;54:76-80. Epub 2018 Jun 19 doi: 10.1016/j.ejim.2018.06.009. PMID: 29934240
Haghpanah S, Zarei T, Eshghi P, Zekavat O, Bordbar M, Hoormand M, Karimi M
Ann Hematol 2018 Oct;97(10):1919-1924. Epub 2018 Jun 21 doi: 10.1007/s00277-018-3392-8. PMID: 29926158
Mohammadi E, Tamaddoni A, Qujeq D, Nasseri E, Zayeri F, Zand H, Gholami M, Mir SM
Phytother Res 2018 Sep;32(9):1828-1835. Epub 2018 May 28 doi: 10.1002/ptr.6118. PMID: 29806132
Karunaratna AMDS, Ranasingha JGS, Mudiyanse RM
Biol Trace Elem Res 2018 Jul;184(1):1-6. Epub 2017 Sep 23 doi: 10.1007/s12011-017-1158-0. PMID: 28940159

Diagnosis

Fragkiadakis K, Ioannou P, Papadakis JA, Hatzidakis A, Gikas A, Kofteridis DP
Jpn J Infect Dis 2018 Sep 21;71(5):370-372. Epub 2018 May 31 doi: 10.7883/yoken.JJID.2018.039. PMID: 29848843
Farooq S, Mazhar W, Siddiqui AJ, Ansari SH, Musharraf SG
Biomed Chromatogr 2018 Jun;32(6):e4200. Epub 2018 Mar 5 doi: 10.1002/bmc.4200. PMID: 29388244
Asadov C, Alimirzoeva Z, Mammadova T, Aliyeva G, Gafarova S, Mammadov J
Int J Hematol 2018 Jul;108(1):5-21. Epub 2018 Jan 29 doi: 10.1007/s12185-018-2411-9. PMID: 29380178
Kalbassi S, Younesi MR, Asgary V
Hematology 2018 Jul;23(6):373-378. Epub 2017 Nov 22 doi: 10.1080/10245332.2017.1404219. PMID: 29165026
Bozdağ M, Bayraktaroğlu S, Aydınok Y, Çallı MC
Acta Radiol 2018 Jun;59(6):732-739. Epub 2017 Sep 7 doi: 10.1177/0284185117730099. PMID: 28882060

Therapy

Klaihmon P, Lertthammakiat S, Anurathapan U, Pakakasama S, Sirachainan N, Hongeng S, Pattanapanyasat K
Thromb Res 2018 Sep;169:8-14. Epub 2018 Jul 4 doi: 10.1016/j.thromres.2018.07.007. PMID: 29990620
Haghpanah S, Zarei T, Eshghi P, Zekavat O, Bordbar M, Hoormand M, Karimi M
Ann Hematol 2018 Oct;97(10):1919-1924. Epub 2018 Jun 21 doi: 10.1007/s00277-018-3392-8. PMID: 29926158
Fragkiadakis K, Ioannou P, Papadakis JA, Hatzidakis A, Gikas A, Kofteridis DP
Jpn J Infect Dis 2018 Sep 21;71(5):370-372. Epub 2018 May 31 doi: 10.7883/yoken.JJID.2018.039. PMID: 29848843
Mohammadi E, Tamaddoni A, Qujeq D, Nasseri E, Zayeri F, Zand H, Gholami M, Mir SM
Phytother Res 2018 Sep;32(9):1828-1835. Epub 2018 May 28 doi: 10.1002/ptr.6118. PMID: 29806132
Kalbassi S, Younesi MR, Asgary V
Hematology 2018 Jul;23(6):373-378. Epub 2017 Nov 22 doi: 10.1080/10245332.2017.1404219. PMID: 29165026

Prognosis

Graffeo L, Vitrano A, Scondotto S, Dardanoni G, Pollina Addario WS, Giambona A, Sacco M, Di Maggio R, Renda D, Taormina F, Triveri A, Attanasio M, Gluud C, Maggio A
Eur J Intern Med 2018 Aug;54:76-80. Epub 2018 Jun 19 doi: 10.1016/j.ejim.2018.06.009. PMID: 29934240
Li XY, Sun X, Chen J, Qin MQ, Luan Z, Zhu YP, Fang JP
World J Pediatr 2018 Feb;14(1):92-99. Epub 2018 Mar 6 doi: 10.1007/s12519-017-0107-5. PMID: 29511925Free PMC Article
Di Maggio R, Hsieh MM, Zhao X, Calvaruso G, Rigano P, Renda D, Tisdale JF, Maggio A
Int J Mol Sci 2018 Feb 28;19(3) doi: 10.3390/ijms19030681. PMID: 29495591Free PMC Article
Kalbassi S, Younesi MR, Asgary V
Hematology 2018 Jul;23(6):373-378. Epub 2017 Nov 22 doi: 10.1080/10245332.2017.1404219. PMID: 29165026
Abaza SE, Abdel-Salam A, Baz AA, Mohamed AA
J Ultrasound 2017 Dec;20(4):301-308. Epub 2017 Nov 1 doi: 10.1007/s40477-017-0264-3. PMID: 29204234Free PMC Article

Clinical prediction guides

Chen JK, Xin XQ, Huang JG
Hemoglobin 2018 May;42(3):159-160. Epub 2018 Sep 25 doi: 10.1080/03630269.2018.1499524. PMID: 30251902
Darvishi-Khezri H, Kosaryan M, Akbarzadeh R, Aliasgharian A, Fazli M
Med Arch 2018 Jun;72(3):170-173. doi: 10.5455/medarh.2018.72.170-173. PMID: 30061760Free PMC Article
Haghpanah S, Zarei T, Eshghi P, Zekavat O, Bordbar M, Hoormand M, Karimi M
Ann Hematol 2018 Oct;97(10):1919-1924. Epub 2018 Jun 21 doi: 10.1007/s00277-018-3392-8. PMID: 29926158
Mohammadi E, Tamaddoni A, Qujeq D, Nasseri E, Zayeri F, Zand H, Gholami M, Mir SM
Phytother Res 2018 Sep;32(9):1828-1835. Epub 2018 May 28 doi: 10.1002/ptr.6118. PMID: 29806132
Karunaratna AMDS, Ranasingha JGS, Mudiyanse RM
Biol Trace Elem Res 2018 Jul;184(1):1-6. Epub 2017 Sep 23 doi: 10.1007/s12011-017-1158-0. PMID: 28940159

Recent systematic reviews

Algiraigri AH, Kassam A
Int J Hematol 2017 Dec;106(6):748-756. Epub 2017 Aug 7 doi: 10.1007/s12185-017-2307-0. PMID: 28786080
Algiraigri AH, Wright NAM, Paolucci EO, Kassam A
Hematol Oncol Stem Cell Ther 2017 Sep;10(3):116-125. Epub 2017 Apr 6 doi: 10.1016/j.hemonc.2017.02.002. PMID: 28408107
Manafikhi H, Drummen G, Palmery M, Peluso I
Crit Rev Oncol Hematol 2017 Feb;110:35-42. Epub 2016 Dec 8 doi: 10.1016/j.critrevonc.2016.12.007. PMID: 28109403
Liaska A, Petrou P, Georgakopoulos CD, Diamanti R, Papaconstantinou D, Kanakis MG, Georgalas I
BMC Ophthalmol 2016 Jul 8;16:102. doi: 10.1186/s12886-016-0285-2. PMID: 27390837Free PMC Article
Zafari M, Kosaryan M, Gill P, Alipour A, Shiran M, Jalalli H, Banihashemi A, Fatahi F
Ann Hematol 2016 Aug;95(8):1341-50. Epub 2016 Mar 12 doi: 10.1007/s00277-016-2620-3. PMID: 26968552

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