Details of Disease

General Information of Disease (ID: DIS5RCQK)

• Disease Name: Beta thalassemia
• Synonyms: erythroblastic anemia; Beta thalassemia intermedia; thalassemia major; Beta thalassemia minor; Thalassemias, beta-; erythroblastic anaemia; thalassemia, Hispanic gamma-delta-beta
• Disease Class: 3A50: Thalassaemia
• Definition: Beta-thalassemia (BT) is characterized by deficiency (Beta+) or absence (Beta0) of synthesis of the beta globin chains of hemoglobin (Hb).
• Disease Hierarchy:
  DISRGY2N: Endocrine disease
  DISQEXHO: Beta-thalassemia and related diseases
  DIS76XZB: Thalassemia
  DIS5RCQK: Beta thalassemia
• ICD Code:
  ICD-11: ICD-11: 3A50.2
  ICD-10: ICD-10: D56.1, D56.3
  Expand ICD-11: '3A50.2
  Expand ICD-10: 'D56.1; 'D56.3
• Disease Identifiers:
  MONDO ID: MONDO_0019402
  MESH ID: D017086
  UMLS CUI: C0005283
  OMIM ID: 613985
  MedGen ID: 2611
  Orphanet ID: 848
  SNOMED CT ID: 65959000

Drug-Interaction Atlas (DIA) of This Disease

This Disease is Treated as An Indication in 3 Approved Drug(s)

Drug Name	Drug ID	Highest Status	Drug Type	REF
Deferasirox	DM6ETS0	Approved	NA	[1]
Deferiprone	DMS2M7O	Approved	Small molecular drug	[2]
Luspatercept	DM715KM	Approved	NA	[3]

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

Drug Name	Drug ID	Highest Status	Drug Type	REF
LentiGlobin	DMSCGM8	Phase 3	NA	[4]
HQK-1001	DM7QUN0	Phase 2	Small molecular drug	[5]
IONIS-TMPRSS6-LRx	DM7VJE1	Phase 2	Antisense oligonucleotide	[6]
LJPC-401	DMVM13R	Phase 2	Peptide	[7]
CTX001	DM90XQC	Phase 1/2	Gene therapy	[8]
OTL-300	DMYGK1D	Phase 1/2	Gene therapy	[9]
ST-400	DM20G71	Phase 1/2	Cell therapy	[10]
SLN124	DMIAOU6	Phase 1	Small interfering RNA	[11]

This Disease is Treated as An Indication in 1 Preclinical Drug(s)

Drug Name	Drug ID	Highest Status	Drug Type	REF
ALN-TMP	DMW7XEU	Preclinical	Small interfering RNA	[12]

Molecular Interaction Atlas (MIA) of This Disease

This Disease Is Related to 25 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
CAD	TT2YT1K	Limited	Biomarker	[13]
DHODH	TTLVP78	Limited	Biomarker	[13]
EPO	TTQG4NR	Limited	Biomarker	[14]
UGT1A1	TT34ZAF	Limited	Genetic Variation	[15]
UMPS	TTAFJUD	Limited	Biomarker	[13]
CACNA1H	TTZPWGN	Disputed	Biomarker	[16]
BACH1	TT2ME4S	Strong	Altered Expression	[17]
BRIP1	TTZV7LJ	Strong	Altered Expression	[17]
CD37	TTFCW29	Strong	Genetic Variation	[18]
CHIT1	TTDYX6T	Strong	Biomarker	[19]
DLL1	TT9CFQD	Strong	Genetic Variation	[20]
ENTPD1	TTYM8DJ	Strong	Genetic Variation	[21]
FCAR	TTGUJAO	Strong	Biomarker	[22]
G6PD	TTKN8W0	Strong	Biomarker	[23]
GSTA1	TT4P8DE	Strong	Genetic Variation	[24]
HAMP	TTRV5YJ	Strong	Biomarker	[25]
IFNL3	TTRF4Q2	Strong	Genetic Variation	[26]
LCN2	TTKTLAI	Strong	Altered Expression	[27]
PGD	TTZ3IFB	Strong	Biomarker	[28]
PSMB6	TT8EPLT	Strong	Genetic Variation	[20]
SCD	TT6RIOV	Strong	Genetic Variation	[29]
SLCO2A1	TTKVTQO	Strong	Biomarker	[30]
SPTBN1	TTS9BDA	Strong	Genetic Variation	[31]
TFRC	TT8MG4S	Strong	Genetic Variation	[32]
HBB	TTM6HK1	Definitive	Autosomal recessive	[33]

This Disease Is Related to 2 DTP Molecule(s)

Gene Name	DTP ID	Evidence Level	Mode of Inheritance	REF
SLC25A20	DTQOUM4	Strong	Genetic Variation	[34]
SLC35A2	DT0567K	Strong	Genetic Variation	[35]

This Disease Is Related to 10 DME Molecule(s)

Gene Name	DME ID	Evidence Level	Mode of Inheritance	REF
PRKCSH	DE073GW	Strong	Biomarker	[36]
UGDH	DE48Q2Z	Strong	Altered Expression	[37]
UGT1A10	DEL5N6Y	Strong	Genetic Variation	[35]
UGT1A3	DEF2WXN	Strong	Genetic Variation	[35]
UGT1A4	DELOY3P	Strong	Genetic Variation	[35]
UGT1A5	DEPF954	Strong	Genetic Variation	[35]
UGT1A6	DESD26P	Strong	Genetic Variation	[35]
UGT1A7	DEZO4N3	Strong	Genetic Variation	[35]
UGT1A8	DE2GB8N	Strong	Genetic Variation	[35]
UGT1A9	DE85D2P	Strong	Genetic Variation	[35]

This Disease Is Related to 40 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
KLF1	OT1FK08U	moderate	Altered Expression	[38]
ANK2	OTWB4R1Y	Strong	Genetic Variation	[31]
AP5Z1	OTXIPLFH	Strong	Genetic Variation	[39]
ATOH8	OT7SY3BN	Strong	Altered Expression	[40]
CD177	OTS79FNF	Strong	Altered Expression	[41]
CRYL1	OT0SJSJM	Strong	Altered Expression	[37]
CUL9	OTPUCLZT	Strong	Biomarker	[42]
ERFE	OTSES1HA	Strong	Altered Expression	[43]
GLUD1	OTXKOCUH	Strong	Altered Expression	[37]
H6PD	OTO7TNDD	Strong	Altered Expression	[37]
HACD1	OTEC7EP7	Strong	Genetic Variation	[44]
HBD	OTRQG4WA	Strong	Genetic Variation	[45]
HBD	OTRQG4WA	Strong	Genetic Variation	[46]
HBE1	OTJPKMX4	Strong	Altered Expression	[47]
HBZ	OTMHGFSS	Strong	Biomarker	[48]
HFE	OTDD93KB	Strong	Genetic Variation	[49]
ITGA2B	OT4Y17PY	Strong	Genetic Variation	[50]
KIDINS220	OTLBH2MA	Strong	Genetic Variation	[51]
KLF10	OT4F4UGS	Strong	Biomarker	[52]
LARP1B	OT9JZ7K5	Strong	Posttranslational Modification	[53]
OPN1MW	OTPJ7LX4	Strong	Genetic Variation	[54]
OR13J1	OT8X7EM0	Strong	Genetic Variation	[55]
PALLD	OTZ2MUJZ	Strong	Genetic Variation	[31]
PMCH	OT3D9SA4	Strong	Genetic Variation	[56]
PSMA5	OT38E6Y1	Strong	Genetic Variation	[39]
RNGTT	OT59E0KX	Strong	Genetic Variation	[57]
SAMD14	OTLDQW51	Strong	Biomarker	[58]
SCLT1	OT2ZSSP4	Strong	Genetic Variation	[57]
SEC23B	OT2NFSIQ	Strong	Biomarker	[59]
SERPINB6	OT7G55IK	Strong	Genetic Variation	[44]
SFMBT2	OTZQT61Q	Strong	Biomarker	[60]
SORBS1	OTWH8762	Strong	Genetic Variation	[44]
SOX6	OTT0W0LE	Strong	Altered Expression	[61]
SPRR2A	OT62ZU6B	Strong	Biomarker	[62]
SPTA1	OT1YMP65	Strong	Genetic Variation	[31]
STK3	OTLNSCQD	Strong	Biomarker	[63]
TFR2	OTMYCCEO	Strong	Biomarker	[64]
THOC5	OTHY50SK	Strong	Biomarker	[65]
HBB	OT514IKQ	Definitive	Autosomal recessive	[33]
SACS	OTZGXQ8A	Definitive	Altered Expression	[66]

References

• [1] Deferasirox FDA Label
• [2] Deferiprone FDA Label
• [3] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [4] ClinicalTrials.gov (NCT03207009) A Study Evaluating the Efficacy and Safety of the LentiGlobin BB305 Drug Product in Subjects With Transfusion-Dependent beta-Thalassemia. U.S. National Institutes of Health.
• [5] A phase 2 trial of HQK-1001 in HbE-beta thalassemia demonstrates HbF induction and reduced anemia. Blood. 2014 Mar 20;123(12):1956-7.
• [6] ClinicalTrials.gov (NCT04059406) Study to Evaluate the Efficacy, Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of IONIS TMPRSS6-LRx. U.S. National Institutes of Health.
• [7] ClinicalTrials.gov (NCT03381833) A Study With LJPC-401 for the Treatment of Myocardial Iron Overload in Adult Patients With Transfusion-Dependent Beta Thalassemia. U.S. National Institutes of Health.
• [8] ClinicalTrials.gov (NCT03655678) A Safety and Efficacy Study Evaluating CTX001 in Subjects With Transfusion-Dependent beta-Thalassemia. U.S. National Institutes of Health.
• [9] ClinicalTrials.gov (NCT03275051) Long-term Follow-up of Subjects Treated With OTL-300 for Transfusion Dependent Beta-thalassemia Study (TIGET-BTHAL). U.S. National Institutes of Health.
• [10] ClinicalTrials.gov (NCT03432364) A Study to Assess the Safety, Tolerability, and Efficacy of ST-400 for Treatment of Transfusion-Dependent Beta-thalassemia (TDT). U.S. National Institutes of Health.
• [11] ClinicalTrials.gov (NCT04718844) A Study Investigate the Safety, Tolerability, Pharmacokinetic, and Pharmacodynamic Response of SLN124 in Adults With Alpha/Beta-thalassaemia and Very Low- and Low-risk Myelodysplastic Syndrome. U.S. National Institutes of Health.
• [12] Targeting iron metabolism in drug discovery and delivery. Nat Rev Drug Discov. 2017 Jun;16(6):400-423.
• [13] 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.
• [14] Mutual Cross Talk Between Iron Homeostasis and Erythropoiesis.Vitam Horm. 2017;105:143-160. doi: 10.1016/bs.vh.2017.01.001. Epub 2017 Mar 15.
• [15] The effect of UGT1A1 promoter polymorphism on bilirubin response to hydroxyurea therapy in hemoglobinopathies.Clin Biochem. 2010 Nov;43(16-17):1329-32. doi: 10.1016/j.clinbiochem.2010.08.006. Epub 2010 Aug 13.
• [16] 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.
• [17] MiR-155 enhances phagocytic activity of -thalassemia/HbE monocytes via targeting of BACH1.Int J Hematol. 2017 Nov;106(5):638-647. doi: 10.1007/s12185-017-2291-4. Epub 2017 Jul 6.
• [18] Molecular detection of Spanish deltabeta-thalassemia associated with beta-thalassemia identified during prenatal diagnosis.Clin Chim Acta. 2006 Jun;368(1-2):195-8. doi: 10.1016/j.cca.2005.12.041. Epub 2006 Feb 9.
• [19] Plasma chitotriosidase activity in patients with beta-thalassemia.Am J Hematol. 2002 Sep;71(1):7-10. doi: 10.1002/ajh.10151.
• [20] The Corfu deltabeta thalassemia deletion disrupts gamma-globin gene silencing and reveals post-transcriptional regulation of HbF expression.Blood. 2005 Mar 1;105(5):2154-60. doi: 10.1182/blood-2003-11-4069. Epub 2004 Nov 9.
• [21] Co-inheritance of novel ATRX gene mutation and globin ( & ) gene mutations in transfusion dependent beta-thalassemia patients.Blood Cells Mol Dis. 2015 Jun;55(1):27-9. doi: 10.1016/j.bcmd.2015.03.008. Epub 2015 Mar 30.
• [22] Beta-thalassemia in the Korean population.Int J Hematol. 2002 Aug;76 Suppl 2:93-5. doi: 10.1007/BF03165096.
• [23] Hemolytic Dynamics of Weekly Primaquine Antirelapse Therapy Among Cambodians With Acute Plasmodium vivax Malaria With or Without Glucose-6-Phosphate Dehydrogenase Deficiency.J Infect Dis. 2019 Oct 22;220(11):1750-1760. doi: 10.1093/infdis/jiz313.
• [24] Influence of glutathione S-transferase gene polymorphisms on busulfan pharmacokinetics and outcome of hematopoietic stem-cell transplantation in thalassemia pediatric patients.Bone Marrow Transplant. 2016 Mar;51(3):377-83. doi: 10.1038/bmt.2015.321. Epub 2015 Dec 21.
• [25] Oral ferroportin inhibitor ameliorates ineffective erythropoiesis in a model of -thalassemia.J Clin Invest. 2019 Dec 9;130(1):491-506. doi: 10.1172/JCI129382.
• [26] IFNL3 polymorphisms and HCV infection in patients with beta thalassemia.Ann Hepatol. 2015 May-Jun;14(3):389-95.
• [27] Upregulation of neutrophil gelatinase-associated lipocalin, NGAL/Lcn2, in beta-thalassemia patients.Arch Med Res. 2008 May;39(4):402-7. doi: 10.1016/j.arcmed.2007.12.002. Epub 2008 Mar 10.
• [28] 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.
• [29] Dietary nonheme iron is equally bioavailable from ferritin or ferrous sulfate in thalassemia intermedia.Pediatr Hematol Oncol. 2017 Nov;34(8):455-467. doi: 10.1080/08880018.2017.1395935. Epub 2017 Dec 12.
• [30] Multiple displacement amplification as the first step can increase the diagnostic efficiency of preimplantation genetic testing for monogenic disease for -thalassemia.J Obstet Gynaecol Res. 2019 Aug;45(8):1515-1521. doi: 10.1111/jog.14003. Epub 2019 May 29.
• [31] Analysis of erythrocyte and platelet membrane proteins in various forms of beta-thalassemia.Biochemistry (Mosc). 2004 Jul;69(7):748-53. doi: 10.1023/b:biry.0000040198.62939.56.
• [32] Detection of three common mutations causing -thalassemia by using a closed-tube multiplex PCR.Exp Mol Pathol. 2018 Oct;105(2):208-212. doi: 10.1016/j.yexmp.2018.08.005. Epub 2018 Aug 15.
• [33] Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020 Feb;22(2):245-257. doi: 10.1038/s41436-019-0686-8. Epub 2019 Nov 6.
• [34] Analyses of beta-thalassemia mutant DNA interactions with erythroid Krppel-like factor (EKLF), an erythroid cell-specific transcription factor.J Biol Chem. 1994 Jan 14;269(2):1493-500.
• [35] 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.
• [36] Brain iron content in systemic iron overload: A beta-thalassemia quantitative MRI study.Neuroimage Clin. 2019;24:102058. doi: 10.1016/j.nicl.2019.102058. Epub 2019 Oct 25.
• [37] Glycerol-3-phosphate dehydrogenase activity in the red cells of patients with thalassemia.Blood. 1980 Apr;55(4):564-9.
• [38] 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.
• [39] The risk of alpha-thalassaemia in offspring of beta-thalassaemia carriers in Hong Kong.Prenat Diagn. 1997 Aug;17(8):733-6.
• [40] Hepcidin suppression in -thalassemia is associated with the down-regulation of atonal homolog 8.Int J Hematol. 2017 Aug;106(2):196-205. doi: 10.1007/s12185-017-2231-3. Epub 2017 Apr 12.
• [41] Increased CD177 (PRV1) expression in thalassaemia and the underlying erythropoietic activity.Br J Haematol. 2008 Apr;141(1):100-4. doi: 10.1111/j.1365-2141.2008.06993.x.
• [42] 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.
• [43] 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.
• [44] A beta-thalassaemia phenotype not linked to the beta-globin cluster in an Italian family.Br J Haematol. 1992 Jun;81(2):283-7. doi: 10.1111/j.1365-2141.1992.tb08221.x.
• [45] Genetic basis of persistent red blood cell microcytosis in the Chinese unexplained by phenotypical testing.J Clin Pathol. 2015 Jan;68(1):69-72. doi: 10.1136/jclinpath-2014-202568. Epub 2014 Oct 28.
• [46] Borderline hemoglobin A(2) levels in northern Thai population: HBB genotypes and effects of coinherited alpha-thalassemia.Blood Cells Mol Dis. 2019 Feb;74:13-17. doi: 10.1016/j.bcmd.2018.10.002. Epub 2018 Oct 4.
• [47] Dynamic posttranscriptional regulation of epsilon-globin gene expression in vivo.Blood. 2007 Jan 15;109(2):795-801. doi: 10.1182/blood-2006-06-027946. Epub 2006 Sep 26.
• [48] Screening for co-existence of -thalassemia in -thalassemia and in HbE heterozygotes via an enzyme-linked immunosorbent assay for Hb Bart's and embryonic -globin chain.Int J Hematol. 2012 Apr;95(4):386-93. doi: 10.1007/s12185-012-1039-4. Epub 2012 Mar 23.
• [49] HFE gene mutations in Brazilian thalassemic patients.Braz J Med Biol Res. 2006 Dec;39(12):1575-80. doi: 10.1590/s0100-879x2006005000041.
• [50] A novel 223kb deletion in the beta-globin gene cluster was identified in a Chinese thalassemia major patient.Int J Lab Hematol. 2019 Aug;41(4):456-460. doi: 10.1111/ijlh.13021. Epub 2019 Apr 4.
• [51] Regional heterogeneity of beta-thalassemia mutations in the multi ethnic Indian population.Blood Cells Mol Dis. 2009 May-Jun;42(3):241-6. doi: 10.1016/j.bcmd.2008.12.006. Epub 2009 Feb 28.
• [52] KLF10 gene expression is associated with high fetal hemoglobin levels and with response to hydroxyurea treatment in -hemoglobinopathy patients.Pharmacogenomics. 2012 Oct;13(13):1487-500. doi: 10.2217/pgs.12.125.
• [53] Hypermethylation of the gene LARP2 for noninvasive prenatal diagnosis of -thalassemia based on DNA methylation profile.Mol Biol Rep. 2012 Jun;39(6):6591-8. doi: 10.1007/s11033-012-1489-z. Epub 2012 Feb 11.
• [54] Rare beta-thalassemia mutations in Asian Indians.Am J Hematol. 2000 Dec;65(4):322-3. doi: 10.1002/1096-8652(200012)65:4<322::aid-ajh14>3.0.co;2-2.
• [55] Mild beta+(-87)-thalassemia CACCC box mutation is associated with elevated fetal hemoglobin expression in cis.Am J Hematol. 1994 Mar;45(3):265-7. doi: 10.1002/ajh.2830450316.
• [56] Genotype and phenotype characterizations in a large cohort of -thalassemia heterozygote with different forms of -thalassemia in northeast Thailand.Blood Cells Mol Dis. 2011 Aug 15;47(2):120-4. doi: 10.1016/j.bcmd.2011.05.003. Epub 2011 Jun 12.
• [57] The clinical significance of the spectrum of interactions of CAP+1 (A-->C), a silent beta-globin gene mutation, with other beta-thalassemia mutations and globin gene modifiers in north Indians.Eur J Haematol. 2007 Nov;79(5):417-21. doi: 10.1111/j.1600-0609.2007.00958.x. Epub 2007 Sep 27.
• [58] GATA Factor-Regulated Samd14 Enhancer Confers Red Blood Cell Regeneration and Survival in Severe Anemia.Dev Cell. 2017 Aug 7;42(3):213-225.e4. doi: 10.1016/j.devcel.2017.07.009.
• [59] Bone marrow transplantation in a case of severe, type II congenital dyserythropoietic anaemia (CDA II).Bone Marrow Transplant. 2001 Jan;27(2):213-5. doi: 10.1038/sj.bmt.1702764.
• [60] Circ-SFMBT2 promotes the proliferation of gastric cancer cells through sponging miR-182-5p to enhance CREB1 expression.Cancer Manag Res. 2018 Nov 16;10:5725-5734. doi: 10.2147/CMAR.S172592. eCollection 2018.
• [61] Inducing indel mutation in the SOX6 gene by zinc finger nuclease for gamma reactivation: An approach towards gene therapy of beta thalassemia.J Cell Biochem. 2018 Mar;119(3):2512-2519. doi: 10.1002/jcb.26412. Epub 2017 Nov 30.
• [62] High-resolution melting analysis for noninvasive prenatal diagnosis of IVS-II-I (G-A) fetal DNA in minor beta-thalassemia mothers.J Matern Fetal Neonatal Med. 2016 Oct;29(20):3323-8. doi: 10.3109/14767058.2015.1124263. Epub 2015 Dec 23.
• [63] A beta-thalassemia lesion abolishes the same Mst II site as the sickle mutation.Nucleic Acids Res. 1983 Nov 25;11(22):7789-94. doi: 10.1093/nar/11.22.7789.
• [64] 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.
• [65] Colla corii asini might upregulate ZNF471 and THOC5 by KRAB domain-containing zinc-finger protein pathway and THO complex subunit 5 pathway to improve anemia of pregnant women with -thalassemia.Ann Hematol. 2019 Aug;98(8):1813-1826. doi: 10.1007/s00277-019-03710-1. Epub 2019 May 16.
• [66] Human genetics: lessons from Quebec populations.Annu Rev Genomics Hum Genet. 2001;2:69-101. doi: 10.1146/annurev.genom.2.1.69.