Causes, Symptoms, Diagnosis and Treatment

1. Hereditary Angioedema
Isac Sugance
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2. GENERAL INFORMATION
NAME – Hereditary Angioedema
Hereditary angioedema is a disorder characterized by recurrent
episodes of severe swelling (angioedema). The most common
areas of the body to develop swelling are the limbs, face, intestinal
tract, and airway.
ALTERNATE NAMES – C1 esterase inhibitor deficiency, C1
inhibitor deficiency, HAE, HANE, hereditary antineurotic edema
MAIN RESPONSIBILITES - All of the genes that causes Hereditary
Angioedema provides instructions for making a protein called C1
inhibitor, which is a type of serine protease inhibitor (serpin). Serpins
help control several types of chemical reactions by blocking the activity
of certain proteins. C1 inhibitor is important for controlling a range of
processes involved in maintaining blood vessels, including inflammation.
Inflammation is a normal body response to infection, irritation, or other
injury
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3. DATA ABOUT GENE
LOCATION OF THE GENE – 11q12.1
LENGTH OF THE GENE – base pairs 57,597,685
to 57,614,848 on chromosome 11
NUMBER OF EXONS / INTRONS – 5 / 4
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4. Cytogenetic location 4

5. NORMAL GENE EXPRESSION
MOLECULAR LEVEL - The SERPING1 gene provides
instructions for making a protein called C1 inhibitor, which is
a type of serine protease inhibitor (serpin).
CELLULAR LEVEL - Serpins help control several types of
chemical reactions by blocking the activity of certain proteins.
C1 inhibitor is important for controlling a range of processes
involved in maintaining blood vessels, including
inflammation. Inflammation is a normal body response to
infection, irritation, or other injury.
ORGANISM LEVEL - C1 inhibitor blocks the activity of several
proteins in the blood, including plasma kallikrein and the
activated form of factor XII (called factor XIIa). These two
proteins are involved in the production of bradykinin.
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6. MUTANT GENE EXPRESSION
MOLECULAR LEVEL – The SERPING1 gene provides
instructions for making a protein called C1 inhibitor.
CELLULAR LEVEL – C1 Inhibitor functions decrease.
ORGANISM LEVEL – Increased production of Bradykinin
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7. MUTATION AND THEIR CONSEQUENCES
• More than 250 mutations in the SERPING1 gene have been
found to cause hereditary angioedema types I and II.
• Mutations that cause type I occur throughout the gene and
lead to reduced levels of C1 inhibitor in the blood.
Mutations that cause type II usually occur in a specific
region of the gene called exon 8 and result in the production
of a C1 inhibitor that functions abnormally. Without the
proper levels of functional C1 inhibitor, the activity of
plasma kallikrein and factor XIIa cannot be blocked and
excessive amounts of bradykinin are produced. Excess fluids
leak through blood vessel walls and accumulate in body
tissues, leading to the recurrent episodes of swelling seen in
individuals with hereditary angioedema type I and type II.
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8. GENEALOGICAL
INHERITANCE
Genotype of affected person – AA, Aa
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9. ANALYSIS
• EXPRESSIVITY - Expressivity is variable as it is
expressed to a different degree among individuals with
the same influence.
• PENETRATION - Penetration is the frequency with
which a heritable trait is manifested by individuals
carrying the principal gene and is observed only in
autosomal dominant inheritance. There is penetration in
SERPING1 gene as it has autosomal dominant
inheritance.
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10. ANALYSIS
• PLEIOTROPY - There is pleiotropy.
• GENETIC HETEROGENEITY –
• locus heterogeneity as there is 250 mutation in SERPING1 genes
are responsible for Hereditary Angioedema working in similar
way.
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11. GENETIC DIAGNOSTIC
• Molecular analysis of gene mutations:
• PCR
• Sequencing
• Southern-blot
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12. PROPHYLAXIS
Hereditary angioedema (HAE) is a rare congenital disorder characterized
by recurrent episodes of subcutaneous or submucosal edema. Laryngeal
manifestations can be life-threatening. In the majority of cases, the disease
can be adequately treated with an on-demand approach--in some cases,
however, short- or long-term prophylaxis is indicated. Attenuated
androgens used to be the drugs of choice, but they are associated with
considerable side effects and no longer commercially available in the
German-speaking countries of the EU. They are currently being replaced
by more effective and more tolerable agents such C1-inhibitors, the
kallikrein inhibitor ecallantide, and the B2 receptor antagonist icatibant,
which have recently obtained market authorization. These new drugs have
had a major impact, especially on the indications and procedures for long-
term prophylaxis. According to the most recent international consensus
papers and our own experience, self-administered C1-inhibitors are now
the first option for long-term prophylactic therapy. The decision for
prophylaxis should no longer be based on single parameters such as the
frequency of attacks but on adequate overall disease control including
quality of life. More drugs are currently being developed, which may lead
to further changes in the treatment algorithms of HAE.
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13. Heriditary Angioedema 13

14. WEBOGRAPHY
• https://ghr.nlm.nih.gov/gene/CHRNE#
• https://www.ncbi.nlm.nih.gov/gtr/conditions/CN11960
8/
• https://ghr.nlm.nih.gov/condition/hereditary-
angioedema#
• https://ghr.nlm.nih.gov/gene/SERPING1#conditions
• https://www.genecards.org/cgi-
bin/carddisp.pl?gene=SERPING1&keywords=serping1
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