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Hereditary angioedema type 3(HAE3)

MedGen UID:
346653
Concept ID:
C1857728
Disease or Syndrome
Synonyms: ANGIONEUROTIC EDEMA, HEREDITARY, WITH NORMAL C1 INHIBITOR CONCENTRATION AND FUNCTION; ESTROGEN-RELATED HAE; ESTROGEN-SENSITIVE HAE; HAE WITH NORMAL C1 INHIBITOR CONCENTRATION AND FUNCTION; HAE3; Hereditary angioedema, type III
Modes of inheritance:
Autosomal dominant inheritance
MedGen UID:
141047
Concept ID:
C0443147
Intellectual Product
Source: 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.
 
Gene (location): F12 (5q35.3)
 
Monarch Initiative: MONDO:0012526
OMIM®: 610618
Orphanet: ORPHA100054

Definition

Hereditary angioedema is a disorder characterized by recurrent episodes of severe swelling (angioedema). The parts of the body that are most often affected by swelling are the limbs, face, intestinal tract, and airway. Minor trauma or stress may trigger an attack, but swelling often occurs without a known trigger. Episodes involving the intestinal tract cause severe abdominal pain, nausea, and vomiting. Swelling in the airway can restrict breathing and lead to life-threatening obstruction of the airway. About one-third of people with this condition develop a non-itchy rash called erythema marginatum during an attack.

Symptoms of hereditary angioedema typically begin in childhood and worsen during puberty.  On average, untreated individuals have swelling episodes every 1 to 2 weeks, and most episodes last for about 3 to 4 days. The frequency and duration of attacks vary greatly among people with hereditary angioedema, even among people in the same family.

Hereditary angioedema is broadly divided into two types, which are distinguished by levels of a protein called C1 inhibitor (C1-INH) in the blood. These types are known as hereditary angioedema due to C1-INH deficiency and hereditary angioedema with normal C1-INH. 

Hereditary angioedema due to C1-INH deficiency is further divided into two types: type I occurs when C1-INH levels are low, and type II occurs when the C1-INH protein is not functioning correctly. 



The different types of hereditary angioedema have similar signs and symptoms.  [from MedlinePlus Genetics]

Clinical features

From HPO
Episodic abdominal pain
MedGen UID:
814352
Concept ID:
C3808022
Finding
An intermittent form of abdominal pain.
Vomiting
MedGen UID:
12124
Concept ID:
C0042963
Sign or Symptom
Forceful ejection of the contents of the stomach through the mouth by means of a series of involuntary spasmic contractions.
Intestinal edema
MedGen UID:
216042
Concept ID:
C1142262
Finding
Accumulation of cell free, noninflammatony fluid within the wall of the intestinal tract producing uniform thickening of the mucosal folds.
Pharyngeal edema
MedGen UID:
66733
Concept ID:
C0236024
Pathologic Function
Abnormal accumulation of fluid leading to swelling of the pharynx.
Episodic upper airway obstruction
MedGen UID:
868579
Concept ID:
C4022978
Finding
Intermittent episodes of increased resistance to the passage of air in the upper airway.
Facial edema
MedGen UID:
154241
Concept ID:
C0542571
Pathologic Function
Swelling due to an excessive accumulation of fluid in facial tissues.
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.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
Follow this link to review classifications for Hereditary angioedema type 3 in Orphanet.

Professional guidelines

PubMed

Šimac DV, Štimac T, Novak S
Curr Allergy Asthma Rep 2022 Oct;22(10):135-140. Epub 2022 Aug 31 doi: 10.1007/s11882-022-01040-3. PMID: 36044174

Curated

Orphanet, Non histamine-induced angioedema, 2009

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