Alpha-1 Antitrypsin Deficiency is a rare disease that affects the luns and liver of people.

1. AlphaAlpha--1 Antitrypsin Deficiency1 Antitrypsin Deficiency
Jimale Mohamed AliJimale Mohamed Ali

2. AlphaAlpha--1 Antitrypsin Deficiency1 Antitrypsin Deficiency
• Alpha-1 Antitrypsin Deficiency (AATD) is a genetic
inherited autosomal-codominant or autosomal
recessive condition.
• AATD is caused by mutations in the SERPINA1 gene
located in the long arm of chromosome 14.
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3. EpidemiologyEpidemiology
• Alpha-1 Antitrypsin deficiency (AAT) is described
throughout the world in all racial
subgroups. Worldwide it is believed there are 116
million carriers and 3.4 million cases of deficiency.
There is a strong belief that many cases of AAT
have gone undiagnosed or misdiagnosed as
emphysema, bronchiectasis, or cirrhosis.
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4. PathophysiologyPathophysiology
• Alpha-1 Antitrypsin is an enzyme produced by the
liver, and goes to the lungs through the blood
stream.
• It protects the lungs from damage by Neutrophil
Elastase (NE).
• Neutrophil Elastase is a protease (breaks down
protein) produced by the WBC.
• This genetic defect alters the configuration of the
alpha1-antitrypsin molecule and prevents its release
from hepatocytes.
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5. • Serum levels of alpha-1 antitrypsin are decreased,
leading to low alveolar concentrations, where the
alpha1-antitrypsin molecule normally would serve as
protection against proteases such neutrophil
elastase. The resulting protease excess in alveoli
destroys alveolar walls and causes emphysema. The
accumulation of excess alpha1-antitrypsin in
hepatocytes can also lead to destruction of these
cells and ultimately, clinical liver disease.
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7. InheritanceInheritance
• Alpha-1 Antitrypsin Deficiency is a single gene
inheritance (Mendelian).
• You inherited an allele from each parent.
Autosomal co-dominant
Autosomal Recessive
AA = A normal child =25%
Aa = A carrier child =50%
aa = An affected child =25%
A a
A AA Aa
a Aa aa
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9. GenotypeGenotype
• There are many variants for alpha1 AT Deficiency.
• Most common is the S variant (SS) others include MS,
MZ, or ZZ.
• The Z variant is due to a substitution on the distal
end of chromosome 14, (Location: 14q32.12 ) worst
variant.
• Most commonly the substitution is Glutamic acid is
replaced by lysine at position 342 (Glu342Lys).
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10. Clinical PresentationClinical Presentation
• In this disease the α-1 AT cannot go to the blood
stream, so it accumulates in the liver, and causes
liver damage like jaundice, cirrhosis, and increased
risk of liver cancer.
• If α-1 AT is not going to the blood stream, it is not
going to the lungs. Now the NE is free to attack the
lungs, and cause lung diseases such as COPD,
Emphysema, Chronic Bronchitis, etc..
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11. Signs and SymptomsSigns and Symptoms
Jaundice
Dyspnea
Cough
Wheezing
Recurrent pulmonary infections
Rapid heartbeat upon standing
Tiredness
Vision problems
Weight loss
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12. DiagnosisDiagnosis
• It is difficult to diagnose this disease because when the
patient has COPD or Emphysema, you don’t think about
Alpha-1 Antitrypsin deficiency.
• More than 90% of cases are not diagnosed.
• At first, many people who have AAT deficiency are
diagnosed with asthma. This is because wheezing also is
a symptom of asthma. Also, people who have AAT
deficiency respond well to asthma medicines.
• You can diagnose by taking a blood test that measures
the level of the enzyme α-1 AT. This test is simple and
highly accurate.
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13. • We don’t test anyone with emphysema, these are
people that you can suspect:
People who develop emphysema at younger age <45.
Non-smokers who develop emphysema at any age.
People with unexplained liver or lung disease.
Family history of chronic lung or liver diseases.
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14. TreatmentTreatment
• Replacing the Alpha-1 Antitrypsin by weekly injections.
• Gene therapy to prevent more damage.
• Treat with Bronchodilators and Steroids to help the patient’s
breathing.
• In most severe cases a liver or lung transplant is
recommended.
• People with this condition should avoid smoking and alcohol
consumption because smoking can exacerbate the damage in
the lungs and alcohol can worsen the damage in the liver.
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15. PrognosisPrognosis
• The major manifestation of AATD in the first two
decades of life is liver disease; pulmonary
manifestations appear later. Lung function appears to
be normal among adolescents.
• Prognosis is dependent on how patients are
identified. Patients found as a result of screening
often have a prognosis near that of healthy people.
Those identified because of their symptoms face a
more limited future.
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16. Advise to patient and his/her familyAdvise to patient and his/her family
• Individuals who are diagnosed with Alpha-1
Antitrypsin Deficiency and their families need
education and information, but they may also need
support in dealing with their feelings or with the
other social impacts of a genetic diagnosis. You as
doctor can provide information about their medical
condition, so the counseling helps them to deal with
the social issues related to Alpha-1 Antitrypsin
Deficiency.
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17. • Before giving them advice you may first ask them
about their personal goals, what resources are
available in his/her area, how many family members
are involved, and what kind of economic impact
Alpha-1 may have on his/her life. In this way, the
advice and information you give fits his/her situation.
• A particular focus on the family can assist affected
individuals, parents and extended family members
deal with the issues of Alpha-1 Antitrypsin
Deficiency.
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18. ContinueContinue
• The patient who have AAT deficiency needs ongoing
medical care, so he has to talk with his/her doctor about
how often he/she should schedule medical visits.
• Take all of the medicines as prescribed, and follow the
treatment plan. Get flu and pneumococcal vaccines to
protect you from illnesses that may worsen the
condition. If you have a lung infection, get treatment
right away.
• Quit Smoking and Avoid Lung Irritants.
• Follow a Healthy Diet.
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19. • When patients are identified as a new case of
homozygous type Z AATD, the issue of heritability
for their children is frequently raised. Since about
95% of individuals carry the MM phenotype, all
children from parents with ZZ and MM type will
carry the MZ type alpha-1-antitrypsin.
• If the parent is not MM, but is carrying a deficient
allele next to the M allele (i.e. MZ), there is a 50%
chance of ZZ genotype for every newborn from
these parents. Prenatal testing is not a routine
procedure due to the low penetration of liver
disease shortly after birth.
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