Details of Disease

General Information of Disease (ID: DISW06BV)

• Disease Name: Beta-thalassemia major
• Synonyms: Cooley's Anemia; Beta thalassemia Major; Mediterranean anemia; Cooley anemia; Mediterranean anaemia; Cooley's Anaemia; Cooley anaemia
• Definition: Beta-thalassemia (BT) major is a severe early-onset form of BT characterized by severe anemia requiring regular red blood cell transfusions.
• Disease Hierarchy:
  DISOIXFU: Beta-thalassemia HBB/LCRB
  DISW06BV: Beta-thalassemia major
• Disease Identifiers:
  MONDO ID: MONDO_0016486
  MESH ID: D017086
  UMLS CUI: C0002875
  MedGen ID: 283
  Orphanet ID: 231214
  SNOMED CT ID: 26682008

Drug-Interaction Atlas (DIA) of This Disease

This Disease is Treated as An Indication in 8 Approved Drug(s)

Drug Name	Drug ID	Highest Status	Drug Type	REF
Betamethasone	DMAHJEF	Approved	Small molecular drug	[1]
Cortisone Acetate	DMG8K57	Approved	Small molecular drug	[2]
Dexamethasone	DMMWZET	Approved	Small molecular drug	[3]
Hydrocortisone	DMGEMB7	Approved	Small molecular drug	[4]
Methylprednisolone	DM4BDON	Approved	Small molecular drug	[5]
Prednisolone	DMQ8FR2	Approved	Small molecular drug	[6]
Prednisone	DM2HG4X	Approved	Small molecular drug	[7]
Triamcinolone	DM98IXF	Approved	Small molecular drug	[8]

Molecular Interaction Atlas (MIA) of This Disease

This Disease Is Related to 15 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
BCL11A	TTR61MW	Limited	Biomarker	[9]
CAD	TT2YT1K	Limited	Biomarker	[10]
DHODH	TTLVP78	Limited	Biomarker	[10]
TFRC	TT8MG4S	Limited	Biomarker	[11]
UGT1A1	TT34ZAF	Limited	Genetic Variation	[12]
UMPS	TTAFJUD	Limited	Biomarker	[10]
CACNA1H	TTZPWGN	Disputed	Biomarker	[13]
HBB	TTM6HK1	Supportive	Autosomal recessive	[14]
HBB	TTM6HK1	moderate	Biomarker	[15]
LCN2	TTKTLAI	moderate	Biomarker	[16]
EPO	TTQG4NR	Strong	Altered Expression	[17]
HAMP	TTRV5YJ	Strong	Biomarker	[18]
IFNL3	TTRF4Q2	Strong	Genetic Variation	[19]
LMO2	TTFX379	Strong	Biomarker	[20]
PGD	TTZ3IFB	Strong	Biomarker	[21]

This Disease Is Related to 1 DTP Molecule(s)

Gene Name	DTP ID	Evidence Level	Mode of Inheritance	REF
SLC35A2	DT0567K	Strong	Genetic Variation	[22]

This Disease Is Related to 9 DME Molecule(s)

Gene Name	DME ID	Evidence Level	Mode of Inheritance	REF
UGT1A6	DESD26P	Limited	Genetic Variation	[23]
UGDH	DE48Q2Z	Strong	Altered Expression	[24]
UGT1A10	DEL5N6Y	Strong	Genetic Variation	[22]
UGT1A3	DEF2WXN	Strong	Genetic Variation	[22]
UGT1A4	DELOY3P	Strong	Genetic Variation	[22]
UGT1A5	DEPF954	Strong	Genetic Variation	[22]
UGT1A7	DEZO4N3	Strong	Genetic Variation	[22]
UGT1A8	DE2GB8N	Strong	Genetic Variation	[22]
UGT1A9	DE85D2P	Strong	Genetic Variation	[22]

This Disease Is Related to 24 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
TFR2	OTMYCCEO	Limited	Biomarker	[11]
HBB	OT514IKQ	Supportive	Autosomal recessive	[14]
CAPS	OTC9GZ2M	Strong	Biomarker	[25]
CRYL1	OT0SJSJM	Strong	Altered Expression	[24]
CUL9	OTPUCLZT	Strong	Biomarker	[26]
ERFE	OTSES1HA	Strong	Altered Expression	[27]
GLUD1	OTXKOCUH	Strong	Altered Expression	[24]
GYPB	OTESHUIX	Strong	Biomarker	[28]
GYPE	OTBHAG6A	Strong	Biomarker	[28]
H6PD	OTO7TNDD	Strong	Altered Expression	[24]
HBG1	OTVL4NSU	Strong	Biomarker	[20]
HBG2	OT4J48JJ	Strong	Biomarker	[20]
HCST	OTILCB4K	Strong	Biomarker	[29]
HJV	OT4235J2	Strong	Biomarker	[30]
IQCB1	OTYQ28V9	Strong	Biomarker	[31]
KLF1	OT1FK08U	Strong	Genetic Variation	[32]
LPCAT3	OTWI96P4	Strong	Biomarker	[33]
PMCH	OT3D9SA4	Strong	Biomarker	[34]
PPRC1	OT6GB3WR	Strong	Biomarker	[35]
PRH1	OTQZ6HX0	Strong	Biomarker	[35]
PRRX1	OTTZK5G8	Strong	Biomarker	[36]
PRRX2	OT8UR4AU	Strong	Biomarker	[36]
KLF10	OT4F4UGS	Definitive	Genetic Variation	[37]
PC	OT6O0V51	Definitive	Biomarker	[38]

References

• [1] Betamethasone FDA Label
• [2] Cortisone acetate FDA Label
• [3] Dexamethasone FDA Label
• [4] Hydrocortisone FDA Label
• [5] Methylprednisolone FDA Label
• [6] Prednisolone FDA Label
• [7] Prednisone FDA Label
• [8] Triamcinolone FDA Label
• [9] Disruption of the BCL11A Erythroid Enhancer Reactivates Fetal Hemoglobin in Erythroid Cells of Patients with -Thalassemia Major.Mol Ther Methods Clin Dev. 2018 Aug 14;10:313-326. doi: 10.1016/j.omtm.2018.08.003. eCollection 2018 Sep 21.
• [10] Elevation of pyrimidine enzyme activities in the RBC of patients with congenital hypoplastic anaemia and their parents.Br J Haematol. 1979 Jul;42(3):381-90. doi: 10.1111/j.1365-2141.1979.tb01146.x.
• [11] mRNA expression of iron regulatory genes in beta-thalassemia intermedia and beta-thalassemia major mouse models.Am J Hematol. 2006 Jul;81(7):479-83. doi: 10.1002/ajh.20549.
• [12] Persistent jaundice in an infant with homozygous beta thalassemia due to co-inherited Crigler-Najjar syndrome.Pediatr Blood Cancer. 2010 Apr;54(4):627-8. doi: 10.1002/pbc.22313.
• [13] Combined iron chelator with N-acetylcysteine exerts the greatest effect on improving cardiac calcium homeostasis in iron-overloaded thalassemic mice.Toxicology. 2019 Nov 1;427:152289. doi: 10.1016/j.tox.2019.152289. Epub 2019 Sep 19.
• [14] Hemoglobinopathies: clinical manifestations, diagnosis, and treatment. Dtsch Arztebl Int. 2011 Aug;108(31-32):532-40. doi: 10.3238/arztebl.2011.0532. Epub 2011 Aug 8.
• [15] Detection of HCV genome in peripheral blood mononuclear cells of Iranian seropositive and HCV RNA negative in plasma of patients with beta-thalassemia major: Occult HCV infection.J Med Virol. 2019 Jan;91(1):107-114. doi: 10.1002/jmv.25279. Epub 2018 Sep 24.
• [16] Evaluation of Renal Function Disorder With Urinary Neutrophil Gelatinase-associated Lipocalin Level in Patients With -Thalassemia Major.J Pediatr Hematol Oncol. 2019 Oct;41(7):507-510. doi: 10.1097/MPH.0000000000001577.
• [17] Investigation of JAK2V617F Mutation Prevalence in Patients with Beta Thalassemia Major.Lab Med. 2020 Mar 10;51(2):176-180. doi: 10.1093/labmed/lmz045.
• [18] Serum Hepcidin as a Diagnostic Marker of Severe Iron Overload in Beta-thalassemia Major.Indian J Pediatr. 2017 Oct;84(10):745-750. doi: 10.1007/s12098-017-2375-4. Epub 2017 Jun 10.
• [19] IFNL3 polymorphisms and HCV infection in patients with beta thalassemia.Ann Hepatol. 2015 May-Jun;14(3):389-95.
• [20] Reciprocal regulation of -globin expression by exo-miRNAs: Relevance to -globin silencing in -thalassemia major.Sci Rep. 2017 Mar 16;7(1):202. doi: 10.1038/s41598-017-00150-7.
• [21] Birth of a healthy infant following trophectoderm biopsy from blastocysts for PGD of beta-thalassaemia major.Hum Reprod. 2005 Jul;20(7):1855-9. doi: 10.1093/humrep/deh893. Epub 2005 May 5.
• [22] Cholelithiasis in thalassemia major.Eur J Haematol. 2009 Jan;82(1):22-5. doi: 10.1111/j.1600-0609.2008.01162.x. Epub 2008 Oct 31.
• [23] Three most common nonsynonymous UGT1A6*2 polymorphisms (Thr181Ala, Arg184Ser and Ser7Ala) and therapeutic response to deferiprone in -thalassemia major patients.Gene. 2013 Dec 1;531(2):301-5. doi: 10.1016/j.gene.2013.08.078. Epub 2013 Sep 11.
• [24] Glycerol-3-phosphate dehydrogenase activity in the red cells of patients with thalassemia.Blood. 1980 Apr;55(4):564-9.
• [25] Effect of serum fibroblast growth factor receptor 2 and CAPS proteins on calcium status in -thalassaemia major patients who are free from overt inflammation.Growth Factors. 2018 Aug;36(3-4):178-185. doi: 10.1080/08977194.2018.1520707. Epub 2018 Oct 30.
• [26] Elevated plasma chemokine CCL18/PARC in beta-thalassemia.Blood Cells Mol Dis. 2005 Nov-Dec;35(3):328-31. doi: 10.1016/j.bcmd.2005.07.006. Epub 2005 Aug 31.
• [27] Erythroferrone, the new iron regulator: evaluation of its levels in Egyptian patients with beta thalassemia.Ann Hematol. 2020 Jan;99(1):31-39. doi: 10.1007/s00277-019-03882-w. Epub 2019 Dec 13.
• [28] Ineffective erythropoiesis in beta-thalassemia major is due to apoptosis at the polychromatophilic normoblast stage.Exp Hematol. 2000 Dec;28(12):1343-53. doi: 10.1016/s0301-472x(00)00555-5.
• [29] Haploidentical haematopoietic stem cell transplantation for thalassaemia major based on an FBCA conditioning regimen.Br J Haematol. 2018 Aug;182(4):554-558. doi: 10.1111/bjh.15438. Epub 2018 Jul 1.
• [30] Downregulation of hepcidin and haemojuvelin expression in the hepatocyte cell-line HepG2 induced by thalassaemic sera.Br J Haematol. 2006 Oct;135(1):129-38. doi: 10.1111/j.1365-2141.2006.06258.x. Epub 2006 Aug 25.
• [31] Neurocognitive dysfunction in children with thalassemia major: psychometric, neurophysiologic and radiologic evaluation.Hematology. 2017 Dec;22(10):617-622. doi: 10.1080/10245332.2017.1338212. Epub 2017 Jun 16.
• [32] A novel mutation in the erythroid transcription factor KLF1 is likely responsible for ameliorating -thalassemia major.Hum Mutat. 2019 Oct;40(10):1768-1780. doi: 10.1002/humu.23817. Epub 2019 Jun 24.
• [33] C3 polymorphism in beta-thalassemia.Acta Haematol. 1984;71(1):45-8. doi: 10.1159/000206507.
• [34] Clinical and haematological evaluation of beta thalassaemia intermedia characterised by unusually low Hb F and increased Hb A2: beta thalassaemia intermedia II.J Med Genet. 1985 Jun;22(3):213-21. doi: 10.1136/jmg.22.3.213.
• [35] Low levels of coagulation inhibitors: A high-risk thrombotic factor in thalassemic patients.Rev Clin Esp (Barc). 2020 Apr;220(3):162-166. doi: 10.1016/j.rce.2019.05.012. Epub 2019 Oct 2.
• [36] Global analysis of erythroid cells redox status reveals the involvement of Prdx1 and Prdx2 in the severity of beta thalassemia.PLoS One. 2018 Dec 6;13(12):e0208316. doi: 10.1371/journal.pone.0208316. eCollection 2018.
• [37] Klf10 Gene, a Secondary Modifier and a Pharmacogenomic Biomarker of Hydroxyurea Treatment Among Patients With Hemoglobinopathies.J Pediatr Hematol Oncol. 2017 Apr;39(3):e155-e162. doi: 10.1097/MPH.0000000000000762.
• [38] Alterations of anticoagulant proteins and soluble endothelial protein C receptor in thalassemia patients of Chinese origin.Thromb Res. 2018 Dec;172:61-66. doi: 10.1016/j.thromres.2018.10.016. Epub 2018 Oct 18.