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Angioedema, hereditary, 8(HAE8)

MedGen UID:
1780930
•Concept ID:
C5543528
•
Disease or Syndrome
Synonyms: ANGIOEDEMA, HEREDITARY, 8; HAE8
 
Gene (location): HS3ST6 (16p13.3)
 
Monarch Initiative: MONDO:0030298
OMIM®: 619367

Definition

Hereditary angioedema-8 (HAE8) is an autosomal dominant disorder characterized clinically by recurrent and self-limited episodes of localised edema in various organs, including the face, tongue, larynx, and extremities. In rare cases, swelling of the tongue or larynx can lead to airway obstruction. Abdominal attacks may also occur, resulting in abdominal pain, vomiting, and diarrhea. The disorder results from enhanced vascular permeability (summary by Bork et al., 2021). For a discussion of genetic heterogeneity of HAE, see 106100. [from OMIM]

Clinical features

From HPO
Abdominal pain
MedGen UID:
7803
•Concept ID:
C0000737
•
Sign or Symptom
An unpleasant sensation characterized by physical discomfort (such as pricking, throbbing, or aching) and perceived to originate in the abdomen.
See: Feature record | Search on this feature
Diarrhea
MedGen UID:
8360
•Concept ID:
C0011991
•
Sign or Symptom
Abnormally increased frequency (usually defined as three or more) loose or watery bowel movements a day.
See: Feature record | Search on this feature
Episodic vomiting
MedGen UID:
333228
•Concept ID:
C1838993
•
Finding
Paroxysmal, recurrent episodes of vomiting.
See: Feature record | Search on this feature
Laryngeal edema
MedGen UID:
6017
•Concept ID:
C0023052
•
Pathologic Function
An abnormal accumulation of fluid and swelling in the tissues of the larynx.
See: Feature record | Search on this feature
Edema of the dorsum of hands
MedGen UID:
752076
•Concept ID:
C2732374
•
Finding
An abnormal accumulation of fluid beneath the skin on the back of the hands.
See: Feature record | Search on this feature
Swollen lip
MedGen UID:
116100
•Concept ID:
C0240211
•
Sign or Symptom
Enlargement of the lip typically due to fluid buildup or inflammation.
See: Feature record | Search on this feature
Facial edema
MedGen UID:
154241
•Concept ID:
C0542571
•
Pathologic Function
Swelling due to an excessive accumulation of fluid in facial tissues.
See: Feature record | Search on this feature
Angioedema
MedGen UID:
1543
•Concept ID:
C0002994
•
Pathologic Function
Rapid swelling (edema) of the dermis, subcutaneous tissue, mucosa and submucosal tissues of the skin of the face, normally around the mouth, and the mucosa of the mouth and/or throat, as well as the tongue during a period of minutes to several hours. The swelling can also occur elsewhere, typically in the hands. Angioedema is similar to urticaria, but the swelling is subcutaneous rather than on the epidermis.
See: Feature record | Search on this feature
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Professional guidelines

PubMed

Cold Urticaria Syndromes: Diagnosis and Management.
Diaz VL, Gribbons KB, Yazdi-Nejad K, Kuemmerle-Deschner J, Wanderer AA, Broderick L, Hoffman HM
J Allergy Clin Immunol Pract 2023 Aug;11(8):2275-2285. Epub 2023 Jun 7 doi: 10.1016/j.jaip.2023.05.040. PMID: 37290539
Hereditary Angioedema: A Review of the Current and Evolving Treatment Landscape.
Betschel SD, Banerji A, Busse PJ, Cohn DM, Magerl M
J Allergy Clin Immunol Pract 2023 Aug;11(8):2315-2325. Epub 2023 Apr 26 doi: 10.1016/j.jaip.2023.04.017. PMID: 37116793
Current medical management of hereditary angioedema: Follow-up survey of US physicians.
Riedl MA, Banerji A, Gower R
Ann Allergy Asthma Immunol 2021 Mar;126(3):264-272. Epub 2020 Oct 26 doi: 10.1016/j.anai.2020.10.009. PMID: 33122123

Recent clinical studies

Etiology

Efficacy and safety of ligelizumab in adults and adolescents with chronic spontaneous urticaria: results of two phase 3 randomised controlled trials.
Maurer M, Ensina LF, Gimenez-Arnau AM, Sussman G, Hide M, Saini S, Grattan C, Fomina D, Rigopoulos D, Berard F, Canonica GW, Rockmann H, Irani C, Szepietowski JC, Leflein J, Bernstein JA, Peter JG, Kulthanan K, Godse K, Ardusso L, Ukhanova O, Staubach P, Sinclair R, Gogate S, Thomsen SF, Tanus T, Ye YM, Burciu A, Barve A, Modi D, Scosyrev E, Hua E, Letzelter K, Varanasi V, Patekar M, Severin T; PEARL-1 and PEARL-2 trial investigators
Lancet 2024 Jan 13;403(10422):147-159. Epub 2023 Nov 23 doi: 10.1016/S0140-6736(23)01684-7. PMID: 38008109
Gene Mutations Linked to Hereditary Angioedema in Solitary Angioedema Patients With Normal C1 Inhibitor.
Bork K, Wulff K, Witzke G, Staubach P, Hardt J, Meinke P
J Allergy Clin Immunol Pract 2023 Aug;11(8):2441-2449. Epub 2023 Feb 12 doi: 10.1016/j.jaip.2023.01.051. PMID: 36787826
Inhibition of Prekallikrein for Hereditary Angioedema.
Fijen LM, Riedl MA, Bordone L, Bernstein JA, Raasch J, Tachdjian R, Craig T, Lumry WR, Manning ME, Alexander VJ, Newman KB, Revenko A, Baker BF, Nanavati C, MacLeod AR, Schneider E, Cohn DM
N Engl J Med 2022 Mar 17;386(11):1026-1033. doi: 10.1056/NEJMoa2109329. PMID: 35294812
Development of the Hereditary Angioedema Rapid Triage Tool.
Betschel S, Avilla E, Kanani A, Kastner M, Keith P, Binkley K, Lacuesta G, Borici-Mazi R, Badiou J, Rowe A, Yang WH, Waserman S
J Allergy Clin Immunol Pract 2020 Jan;8(1):310-317.e3. Epub 2019 Jun 22 doi: 10.1016/j.jaip.2019.05.056. PMID: 31238160
Methylphenidate for attention deficit hyperactivity disorder (ADHD) in children and adolescents - assessment of adverse events in non-randomised studies.
Storebø OJ, Pedersen N, Ramstad E, Kielsholm ML, Nielsen SS, Krogh HB, Moreira-Maia CR, Magnusson FL, Holmskov M, Gerner T, Skoog M, Rosendal S, Groth C, Gillies D, Buch Rasmussen K, Gauci D, Zwi M, Kirubakaran R, Håkonsen SJ, Aagaard L, Simonsen E, Gluud C
Cochrane Database Syst Rev 2018 May 9;5(5):CD012069. doi: 10.1002/14651858.CD012069.pub2. PMID: 29744873Free PMC Article

Diagnosis

Angioedema With Normal Complement Studies: What Do We Know?
Katelaris CH, Grumach AS, Bork K
J Allergy Clin Immunol Pract 2023 Aug;11(8):2309-2314. Epub 2023 Jun 19 doi: 10.1016/j.jaip.2023.06.022. PMID: 37343921
Cold Urticaria Syndromes: Diagnosis and Management.
Diaz VL, Gribbons KB, Yazdi-Nejad K, Kuemmerle-Deschner J, Wanderer AA, Broderick L, Hoffman HM
J Allergy Clin Immunol Pract 2023 Aug;11(8):2275-2285. Epub 2023 Jun 7 doi: 10.1016/j.jaip.2023.05.040. PMID: 37290539
Genetic Variants Leading to Urticaria and Angioedema and Associated Biomarkers.
Lyons JJ, Farkas H, Germenis AE, Rijavec M, Smith TD, Valent P
J Allergy Clin Immunol Pract 2023 Aug;11(8):2286-2301. Epub 2023 May 30 doi: 10.1016/j.jaip.2023.05.031. PMID: 37263349
Hereditary Angioedema: A Review of the Current and Evolving Treatment Landscape.
Betschel SD, Banerji A, Busse PJ, Cohn DM, Magerl M
J Allergy Clin Immunol Pract 2023 Aug;11(8):2315-2325. Epub 2023 Apr 26 doi: 10.1016/j.jaip.2023.04.017. PMID: 37116793
Gene Mutations Linked to Hereditary Angioedema in Solitary Angioedema Patients With Normal C1 Inhibitor.
Bork K, Wulff K, Witzke G, Staubach P, Hardt J, Meinke P
J Allergy Clin Immunol Pract 2023 Aug;11(8):2441-2449. Epub 2023 Feb 12 doi: 10.1016/j.jaip.2023.01.051. PMID: 36787826

Therapy

Angioedema With Normal Complement Studies: What Do We Know?
Katelaris CH, Grumach AS, Bork K
J Allergy Clin Immunol Pract 2023 Aug;11(8):2309-2314. Epub 2023 Jun 19 doi: 10.1016/j.jaip.2023.06.022. PMID: 37343921
Hereditary Angioedema: A Review of the Current and Evolving Treatment Landscape.
Betschel SD, Banerji A, Busse PJ, Cohn DM, Magerl M
J Allergy Clin Immunol Pract 2023 Aug;11(8):2315-2325. Epub 2023 Apr 26 doi: 10.1016/j.jaip.2023.04.017. PMID: 37116793
Inhibition of Prekallikrein for Hereditary Angioedema.
Fijen LM, Riedl MA, Bordone L, Bernstein JA, Raasch J, Tachdjian R, Craig T, Lumry WR, Manning ME, Alexander VJ, Newman KB, Revenko A, Baker BF, Nanavati C, MacLeod AR, Schneider E, Cohn DM
N Engl J Med 2022 Mar 17;386(11):1026-1033. doi: 10.1056/NEJMoa2109329. PMID: 35294812
Long-term prevention of hereditary angioedema attacks with lanadelumab: The HELP OLE Study.
Banerji A, Bernstein JA, Johnston DT, Lumry WR, Magerl M, Maurer M, Martinez-Saguer I, Zanichelli A, Hao J, Inhaber N, Yu M, Riedl MA; HELP OLE Investigators
Allergy 2022 Mar;77(3):979-990. Epub 2021 Aug 13 doi: 10.1111/all.15011. PMID: 34287942Free PMC Article
8. Hereditary angioedema.
Frank MM
J Allergy Clin Immunol 2008 Feb;121(2 Suppl):S398-401; quiz S419. doi: 10.1016/j.jaci.2007.07.057. PMID: 18241690

Prognosis

How Does Pregnancy and Type of Delivery Affect the Clinical Course of Hereditary Angioedema?
Eyice Karabacak D, Can A, Demir S, Yegit OO, Colakoglu B, Buyukozturk S, Gelincik AA
Int Arch Allergy Immunol 2023;184(12):1216-1224. Epub 2023 Sep 6 doi: 10.1159/000531074. PMID: 37673053
COVID-19 and hereditary angioedema: Incidence, outcomes, and mechanistic implications.
Veronez CL, Christiansen SC, Smith TD, Riedl MA, Zuraw BL
Allergy Asthma Proc 2021 Nov 1;42(6):506-514. doi: 10.2500/aap.2021.42.210083. PMID: 34871158Free PMC Article
Hereditary Angioedema with and Without C1-Inhibitor Deficiency in Postmenopausal Women.
Billebeau A, Fain O, Launay D, Boccon-Gibod I, Bouillet L, Gobert D, Plu-Bureau G, Gompel A; French National Reference Center for Hereditary Angioedema (CREAK)
J Clin Immunol 2021 Jan;41(1):163-170. Epub 2020 Oct 31 doi: 10.1007/s10875-020-00902-7. PMID: 33130967
Development of the Hereditary Angioedema Rapid Triage Tool.
Betschel S, Avilla E, Kanani A, Kastner M, Keith P, Binkley K, Lacuesta G, Borici-Mazi R, Badiou J, Rowe A, Yang WH, Waserman S
J Allergy Clin Immunol Pract 2020 Jan;8(1):310-317.e3. Epub 2019 Jun 22 doi: 10.1016/j.jaip.2019.05.056. PMID: 31238160
Benefits and risks of danazol in hereditary angioedema: a long-term survey of 118 patients.
Bork K, Bygum A, Hardt J
Ann Allergy Asthma Immunol 2008 Feb;100(2):153-61. doi: 10.1016/S1081-1206(10)60424-3. PMID: 18320917

Clinical prediction guides

Efficacy and safety of ligelizumab in adults and adolescents with chronic spontaneous urticaria: results of two phase 3 randomised controlled trials.
Maurer M, Ensina LF, Gimenez-Arnau AM, Sussman G, Hide M, Saini S, Grattan C, Fomina D, Rigopoulos D, Berard F, Canonica GW, Rockmann H, Irani C, Szepietowski JC, Leflein J, Bernstein JA, Peter JG, Kulthanan K, Godse K, Ardusso L, Ukhanova O, Staubach P, Sinclair R, Gogate S, Thomsen SF, Tanus T, Ye YM, Burciu A, Barve A, Modi D, Scosyrev E, Hua E, Letzelter K, Varanasi V, Patekar M, Severin T; PEARL-1 and PEARL-2 trial investigators
Lancet 2024 Jan 13;403(10422):147-159. Epub 2023 Nov 23 doi: 10.1016/S0140-6736(23)01684-7. PMID: 38008109
Increased thromboinflammatory load in hereditary angioedema.
Gramstad OR, Schjalm C, Mollnes TE, Nielsen EW
Clin Exp Immunol 2023 Dec 12;214(2):170-181. doi: 10.1093/cei/uxad091. PMID: 37561062Free PMC Article
The Disease Burden and Societal Costs of Hereditary Angioedema.
Fijen LM, Klein PCG, Cohn DM, Kanters TA
J Allergy Clin Immunol Pract 2023 Aug;11(8):2468-2475.e2. Epub 2023 Mar 27 doi: 10.1016/j.jaip.2023.03.032. PMID: 36990433
Inhibition of Prekallikrein for Hereditary Angioedema.
Fijen LM, Riedl MA, Bordone L, Bernstein JA, Raasch J, Tachdjian R, Craig T, Lumry WR, Manning ME, Alexander VJ, Newman KB, Revenko A, Baker BF, Nanavati C, MacLeod AR, Schneider E, Cohn DM
N Engl J Med 2022 Mar 17;386(11):1026-1033. doi: 10.1056/NEJMoa2109329. PMID: 35294812
Long-term prevention of hereditary angioedema attacks with lanadelumab: The HELP OLE Study.
Banerji A, Bernstein JA, Johnston DT, Lumry WR, Magerl M, Maurer M, Martinez-Saguer I, Zanichelli A, Hao J, Inhaber N, Yu M, Riedl MA; HELP OLE Investigators
Allergy 2022 Mar;77(3):979-990. Epub 2021 Aug 13 doi: 10.1111/all.15011. PMID: 34287942Free PMC Article

Recent systematic reviews

Experience with Intravenous Plasma-Derived C1-Inhibitor in Pregnant Women with Hereditary Angioedema: A Systematic Literature Review.
Brooks JP, Radojicic C, Riedl MA, Newcomer SD, Banerji A, Hsu FI
J Allergy Clin Immunol Pract 2020 Jun;8(6):1875-1880.e3. Epub 2020 Apr 3 doi: 10.1016/j.jaip.2020.03.009. PMID: 32251736
Methylphenidate for attention deficit hyperactivity disorder (ADHD) in children and adolescents - assessment of adverse events in non-randomised studies.
Storebø OJ, Pedersen N, Ramstad E, Kielsholm ML, Nielsen SS, Krogh HB, Moreira-Maia CR, Magnusson FL, Holmskov M, Gerner T, Skoog M, Rosendal S, Groth C, Gillies D, Buch Rasmussen K, Gauci D, Zwi M, Kirubakaran R, Håkonsen SJ, Aagaard L, Simonsen E, Gluud C
Cochrane Database Syst Rev 2018 May 9;5(5):CD012069. doi: 10.1002/14651858.CD012069.pub2. PMID: 29744873Free PMC Article

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      Related information in NCBI Gene
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      Related information in GTR
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      Clinical tests in GTR
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      OMIM records containing genes associated with phenotypes registered in MedGen
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