Details of Disease

General Information of Disease (ID: DIS8X53J)

• Disease Name: Hereditary angioedema
• Synonyms: deficiency of C1 esterase inhibitor; angioedema, hereditary; HAE; hereditary angioneurotic edema; hereditary bradykinine-induced angioedema; HANE; hereditary angioneurotic oedema; familial angioneurotic oedema; hereditary non histamine-induced angioedema; familial angioneurotic edema; hereditary angioedema
• Disease Class: 4A00: Innate/adaptive immunodeficiency
• Definition: Hereditary angioedema (HAE) is a genetic disease characterized by the occurrence of transitory and recurrent subcutaneous and/or submucosal edemas resulting in swelling and/or abdominal pain.
• Disease Hierarchy:
  DIS90QDN: Angioedema
  DISSCALK: Hereditary skin disorder
  DIS8X53J: Hereditary angioedema
• ICD Code:
  ICD-11: ICD-11: 4A00.14
  ICD-9: ICD-9: 277.6
  Expand ICD-11: '4A00.14
  Expand ICD-9: 277.6
• Disease Identifiers:
  MONDO ID: MONDO_0019623
  MESH ID: D054179
  UMLS CUI: C0019243
  MedGen ID: 9229
  Orphanet ID: 91378
  SNOMED CT ID: 82966003

Drug-Interaction Atlas (DIA) of This Disease

This Disease is Treated as An Indication in 6 Approved Drug(s)

Drug Name	Drug ID	Highest Status	Drug Type	REF
Berotralstat	DMWA2DZ	Approved	Small molecular drug	[1]
Cinryze	DMVIKJZ	Approved	NA	[2]
Icatibant	DMQPTOZ	Approved	Small molecular drug	[3]
Lanadelumab	DMEH7YU	Approved	NA	[4]
Rhucin	DM3ADGP	Approved	Small molecular drug	[5]
Stanozolol	DMN1RMO	Approved	Small molecular drug	[6]

This Disease is Treated as An Indication in 5 Clinical Trial Drug(s)

Drug Name	Drug ID	Highest Status	Drug Type	REF
CSL312	DMV574J	Phase 3	Antibody	[7]
Donidalorsen	DMD9LWN	Phase 3	Ligand-conjugated antisense	[8]
Remune	DMFLECG	Phase 3	NA	[9]
Avoralstat	DM5YHU2	Phase 2/3	NA	[10]
AGS-348	DMDUIO4	Phase 1	NA	[11]

Molecular Interaction Atlas (MIA) of This Disease

This Disease Is Related to 7 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
KLKB1	TTN0PCX	Limited	Biomarker	[12]
PLG	TTP86E2	moderate	Genetic Variation	[13]
ANGPT1	TTWNQ1T	Strong	Genetic Variation	[14]
BDKRB2	TTGY8IW	Strong	Genetic Variation	[15]
C1S	TT7LRQH	Strong	Biomarker	[16]
MASP2	TTR01E9	Strong	Biomarker	[17]
RBPJ	TT72D4Z	Strong	Genetic Variation	[18]

This Disease Is Related to 10 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
GRK6	OT4LZTP9	Limited	CausalMutation	[19]
SERPINA4	OTBK0GG7	Disputed	Genetic Variation	[20]
SPINK6	OTYKZANJ	Disputed	Genetic Variation	[20]
C4orf3	OT6TFN1O	Strong	Biomarker	[21]
CSHL1	OTQKU2F5	Strong	Genetic Variation	[18]
INA	OT1D33T4	Strong	Biomarker	[22]
RO60	OTLGM5A8	Strong	Biomarker	[23]
SERPINF2	OTZGAF8B	Strong	Altered Expression	[24]
SMPX	OTLSHGBF	Strong	Genetic Variation	[18]
SSB	OTCCTPBR	Strong	Biomarker	[23]

References

• [1] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2020
• [2] Emerging drug candidates of dipeptidyl peptidase IV (DPP IV) inhibitor class for the treatment of Type 2 Diabetes. Curr Drug Targets. 2009 Jan;10(1):71-87.
• [3] URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 667).
• [4] 2018 FDA drug approvals.Nat Rev Drug Discov. 2019 Feb;18(2):85-89.
• [5] Mullard A: 2010 FDA drug approvals. Nat Rev Drug Discov. 2011 Feb;10(2):82-5.
• [6] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [7] ClinicalTrials.gov (NCT04656418) CSL312 (Garadacimab) in the Prevention of Hereditary Angioedema Attacks. U.S. National Institutes of Health.
• [8] ClinicalTrials.gov (NCT05392114) An Open-Label, Long Term Safety and Efficacy Study of Donidalorsen in the Prophylactic Treatment of Hereditary Angioedema (HAE). U.S.National Institutes of Health.
• [9] ClinicalTrials.gov (NCT00005002) Effectiveness of Treating HIV-Positive Patients With an HIV Vaccine (Remune). U.S. National Institutes of Health.
• [10] ClinicalTrials.gov (NCT02303626) 12-Week Safety and Efficacy Study of BCX4161 as an Oral Prophylaxis Against HAE Attacks. U.S. National Institutes of Health.
• [11] Biopharmaceutical Research Companies Are Developing More Than 430 Medicines for Top Chronic Diseases Affecting Older Americans. Pharmaceutical Research and Manufacturers of America report. 2014.
• [12] Structures of full-length plasma kallikrein bound to highly specific inhibitors describe a new mode of targeted inhibition.J Struct Biol. 2019 May 1;206(2):170-182. doi: 10.1016/j.jsb.2019.03.001. Epub 2019 Mar 12.
• [13] Identification of the recently described plasminogen gene mutation p.Lys330Glu in a family from Northern Germany with hereditary angioedema.Clin Transl Allergy. 2019 Feb 14;9:9. doi: 10.1186/s13601-019-0247-x. eCollection 2019.
• [14] Hereditary angioedema: a Chinese perspective.Eur J Dermatol. 2019 Feb 1;29(1):14-20. doi: 10.1684/ejd.2018.3487.
• [15] Analysis of an exon 1 polymorphism of the B2 bradykinin receptor gene and its transcript in normal subjects and patients with C1 inhibitor deficiency.J Allergy Clin Immunol. 1997 Jan;99(1 Pt 1):134-46. doi: 10.1016/s0091-6749(97)70310-5.
• [16] The Effectiveness and Value of Lanadelumab and C1 Esterase Inhibitors for Prophylaxis of Hereditary Angioedema Attacks.J Manag Care Spec Pharm. 2019 Feb;25(2):143-148. doi: 10.18553/jmcp.2019.25.2.143.
• [17] Complement deficiency and disease: an update.Mol Immunol. 2006 Jan;43(1-2):78-85. doi: 10.1016/j.molimm.2005.06.025.
• [18] Population pharmacokinetics of subcutaneous C1-inhibitor for prevention of attacks in patients with hereditary angioedema.Clin Exp Allergy. 2018 Oct;48(10):1325-1332. doi: 10.1111/cea.13220. Epub 2018 Aug 26.
• [19] Characterization of patients with angioedema without wheals: the importance of F12 gene screening.Clin Immunol. 2015 Apr;157(2):239-48. doi: 10.1016/j.clim.2015.02.013. Epub 2015 Mar 2.
• [20] Novel MASP-2 inhibitors developed via directed evolution of human TFPI1 are potent lectin pathway inhibitors.J Biol Chem. 2019 May 17;294(20):8227-8237. doi: 10.1074/jbc.RA119.008315. Epub 2019 Apr 5.
• [21] An investigational RNAi therapeutic targeting Factor XII (ALN-F12) for the treatment of hereditary angioedema.RNA. 2019 Feb;25(2):255-263. doi: 10.1261/rna.068916.118. Epub 2018 Nov 21.
• [22] Interaction between C1-INA, coagulation, fibrinolysis and kinin system in hereditary angioneurotic edema (HANE) and urticaria.Arch Dermatol Res. 1984;276(6):375-80. doi: 10.1007/BF00413358.
• [23] Association of Sjgren's syndrome with hereditary angioneurotic edema: report of a case.Clin Immunol Immunopathol. 1997 Jul;84(1):95-7. doi: 10.1006/clin.1997.4347.
• [24] Elevated plasmin-alpha 2-antiplasmin complex levels in hereditary angioedema: evidence for the in vivo efficiency of the intrinsic fibrinolytic system.Thromb Res. 1985 Dec 15;40(6):817-21. doi: 10.1016/0049-3848(85)90318-4.