An overview of Alpha-1: from how it's inherited to how it affects the patient and how it is treated.

1. Alpha-1 Antitrypsin Deficiency
By: Sandra Tindle, RRT, CardioPulmonary Rehabilitation
Coordinator

2. What is Alpha-1 Antitrypsin
Deficiency?

3. What is Alpha-1 Antitrypsin
Deficiency?
It is a genetic condition, passed from the
parents to the children.
People with Alpha-1 have received 2 abnormal
Alpha-1 Antitrypsin genes, 1 from their
mother and 1 from their father.
It can result in serious lung disease in adults.
It can result in liver disease at any age.

4. The Abnormal Alpha-1 Genes

5. The Abnormal Alpha-1 Genes
There are many types of abnormal Alpha-1 genes.
The most common abnormal genes are called S
and Z.
Most people with Alpha-1 usually have two Z
genes.
Another deficient combination is SZ although
people with this gene combination are less likely
to have lung or liver problems than those with
two Z genes.

6. The Abnormal Alpha-1 Genes

7. What Happens in Alpha-1 Lung
Disease?

8. What happens in Alpha-1 Lung
Disease?
Alpha-1 Antitrypsin is a protein that is made
mainly in the liver.
The Alpha-1 Antitrypsin isn’t made properly and
gets trapped in the liver, which leads to liver
disease.
This leads to a lack of Alpha-1 in the blood, which
leads to lung disease
The main function of Alpha-1 is to protect the
lungs from inflammation caused by irritants and
infection.

9. What Happens in Alpha-1 Lung
Disease?
WBCs in the lung make an enzyme called
neutrophil elastase that destroys invading germs
and digests damaged or aging cells. In most
people, the Alpha-1 protein neutralizes the
enzyme after a short time.
In Alphas there isn’t enough of the Alpha-1
protein in the lungs, so the enzyme keeps
working, attacking and destroying normal lung
tissue and lung disease develops.
Alphas who smoke are at a much greater risk of
COPD than most people.

10. What Happens in Alpha-1 Lung
Disease?
Alphas often develop COPD in their 30s or 40s,
while people who don’t have Alpha-1 usually
don’t develop COPD symptoms until they are
in their 60s or 70s.
Alphas often develop COPD primarily in the
lower part of their lungs, whereas most non-
Alphas, especially smokers, show the worst
COPD damage in the top part of their lungs.

11. What Happens in Alpha-1 Lung
Disease?

12. What Happens in Alpha-1 Lung
Disease?
Alpha-1 lung problems don’t usually occur in
children, but it is very important for children
with Alpha-1 to avoid all exposure to cigarette
smoke or heavy air pollution to protect their
lungs.
Sometimes children with Alpha-1 can have
severe asthma

13. The Most Common Signs and
Symptoms of Alpha-1 Lung Disease

14. The Most Common Signs and
Symptoms of Alpha-1 Lung Disease
Shortness of Breath
Wheezing
Chronic Bronchitis
Recurring Chest Colds
Less Exercise Tolerance
Asthma that can’t be completely reversed with
aggressive medical treatment
Year round allergies
Bronchiectasis

15. Alpha-1 Facts

16. Alpha-1 Facts
Alpha-1 has been diagnosed in almost all
ethnic groups.
About 1/2500 Americans have Alpha-1.
Alphas may remain healthy throughout their
lives, but early diagnosis and avoiding risk
factors can help prevent Alpha-1 from causing
disease.
About 19,000,000 people in the U.S. are
Alpha-1 carriers.

17. Alpha-1 Facts
 About 100,000 people in the U.S. have Alpha-1
 Many Alphas with ZZ or SZ genes are healthy
 Alpha-1 is the most common genetic risk factor for
emphysema.
 Up to 3% of all people diagnosed with COPD may have
undiagnosed Alpha-1.
 Alpha-1 can also lead to liver disease. The most serious
liver diseases are cirrhosis and liver CA.
 There is a wide variation in how sick people get from
Alpha-1. Some patients have severe disease, while
some have little to none.

18. Diagnosing Alpha-1

19. Diagnosing Alpha-1
Alpha-1 can only be diagnosed by a blood test.
The World Health Organization, American
Thoracic Society, and COPD foundation
recommend that everyone with COPD be
tested for Alpha-1.
Alpha-1 is often first diagnosed as asthma or
smoking related COPD.

20. Treatment for Alpha-1 Lung Disease

21. Treatment for Alpha-1 Lung Disease

22. Treatment for Alpha-1 Lung Disease

23. Treatment for Alpha-1 Lung Disease
There is no cure for Alpha-1
Alphas with lung diseases such as asthma or
COPD can be helped by the same drugs that
are used by non-Alphas for these conditions.
These include bronchodilators and
corticosteroids
Infections are usually treated aggressively
with antibiotics

24. Augmentation Therapy

25. Augmentation Therapy
Weekly IV infusions of the Alpha-1 protein from
purified healthy plasma donors to increase the
level of the Alpha-1 protein in the blood and
lungs to slow or stop the progression of Alpha-1
lung disease.
There are currently 4 medications available for
use in augmentation therapy: Prolastin-C, Aralast
NP, Zemaira, and Glassia.
Has been shown to increase blood and lung levels
of Alpha-1 and reduce the rate of progression of
Alpha-1 lung disease and improved survival.

26. Augmentation Therapy
Cannot restore lost function and is not a cure,
but is currently standard therapy for Alphas
with COPD.
Augmentation therapy is also effective for the
Alpha-1 related skin disease Necrotizing
Panniculitis.
Augmentation therapy does not work for
Alpha-1 liver disease.

27. Augmentation Therapy

28. Safety of Augmentation Therapy

29. Safety of Augmentation Therapy
Augmentation therapy is prepared from
pooled human blood plasma that has been
screened for hepatitis A, B, C and tested for
HIV as well as other infectious viruses.
Side effects: headaches, muscle and joint pain,
and temporary flu- like symptoms. Alphas with
edema or heart failure may have worsening of
their shortness of breath.

30. Children and Alpha-1 Liver Disease

31. Children and Alpha-1 Liver Disease
1/20 babies born with Alpha-1 will have liver
disease, sometimes sever, in the first year of life.
1/14 will have blood tests showing that the liver
is being injured, but the infants look and feel fine.
In most children with abnormal blood tests, the
liver disease improves by itself by the time these
children reach their teens and they remain
healthy.

32. Children and Alpha-1 Liver Disease
Alphas have a 30-40% chance of developing
liver problems during their lifetime.
Avoiding alcohol, maintaining a healthy
weight, getting vaccinated against infections
that damage the liver, and eating a healthy
diet are important.

33. Children and Alpha-1

34. Treatment for Alpha-1 Liver Disease

35. Treatment for Alpha-1 Liver Disease
When treating Alpha-1 liver disease, the focus
is on treating the symptoms and keeping the
patient as healthy as they can be and
preventing health problems.
Treatments are available for intestinal
bleeding, fluid in the abdomen, nutrition and
other problems from scarring of the liver.

36. The Liver in Alpha-1

37. The Liver in Alpha-1
Alpha-1 can cause liver problems at any age.
Large amounts of the Alpha-1 Antitrypsin protein
are made in the liver; nearly 85% of the protein
get stuck in the liver.
The liver gradually gets damaged and scarred
There is no way to prevent the abnormal AAT
from getting stuck in the liver.
The lack of AAT in the blood allows the lungs to
get damaged by smoke and air pollution and can
show up as lung disease with Alpha-1.

38. The Most Common Signs and
Symptoms of Alpha-1 Liver Disease

39. The Most Common Signs and
Symptoms of Alpha-1 Liver Disease
Unexplained liver disease or elevated liver
enzymes
Eyes and skin turning yellow (jaundice)
Swelling of the abdomen or legs
Vomiting blood (enlarged veins in the
esophagus or stomach)
In babies: jaundice, swelling of the abdomen,
and poor growth, diarrhea

40. The Most Common Signs and
Symptoms of Alpha-1 Liver Disease
Feeling weak and tired
Most Alphas have no symptoms of liver
disease

41. Testing for Alpha-1

42. Testing for Alpha-1
The Alpha-1 Foundation encourages testing
for Alpha-1 for those who are at a high risk for
the genetic disorder.
It is recommended that anyone diagnosed
with the following diseases be tested for
Alpha-1: COPD, asthma that is incompletely
irreversible after aggressive treatment,
chronic liver disease, unexplained liver disease
in infants and children.

43. Testing for Alpha-1
Anyone can ask their doctor to test them for
Alpha-1, or choose to be tested confidentially
through the Foundation’s Alpha-1 coded
testing study.

44. Resources
The Alpha-1 Foundation: www.alpha1.org
The National Human Genome Research
Institute: www.genome.gov
Boston University: www.bu.edu
Cleveland Clinic:
www.clevelandclinicmeded.com