Research Registry FAQs

Who is eligible to enroll in the Alpha-1 Research Registry?
Individuals of all ages who are diagnosed with Alpha-1 Antitrypsin Deficiency and individuals identified as carriers of Alpha-1 Antitrypsin Deficiency are encouraged to enroll in the Research Registry.
Who will have access to my name? How confidential is this database?
Your questionnaire will go directly to the Registry Coordinating Center at the Medical University of South Carolina, which is under the academic supervision of the University system. This supervision includes strict adherence to established confidentiality procedures that are intended to protect the identity of those who participate.

The Registry is required to conceal a member's identity and personal information from researchers and organizations unless consent is granted by the Registry member. The database is kept under tight security at all times. This means that it is password protected and inaccessible from the Internet. Also, all hard copies of personal information are kept under lock and key. Only the Registry Director and Coordinators have access to a member's personal information.
What can I expect if I enroll in the Registry or in any research study?
The first thing you will need to do is provide your informed consent. During this process, you should read the details of the invitation. If you do not understand any aspect of the study, you should ask the study staff to explain the study to you and address your questions and concerns before you make decisions. 

Once you have given your consent to participate in a study, you are considered enrolled and you may proceed with the outlined study activities. Some of these activities may be interviews, surveys, medical tests, educational sessions, or the administration of certain treatments.
Who sponsors research?

The list of research sponsors is very large and includes both public and private sources. Every study should state the funding source. Some small studies may be unfunded.  Some of the common sponsors include:
  • The U.S. Department of Health and Human Services, including the National Institutes of Health.
  • Pharmaceutical Manufacturers
  • Biotechnology Companies
  • Not-for-profit organizations, such as the Alpha-1 Foundation

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ACT Study FAQs

What is the ACT Study?
The Alpha-1 Coded Testing (ACT) Study is a free and confidential research study that includes a research questionnaire and an Alpha-1 finger-stick testing kit. ACT provides a way for those at risk for Alpha-1 Antitrypsin Deficiency (Alpha-1), including family members of already-diagnosed Alphas, to learn their Alpha-1 genotype. The genotype is the pair of genes an individual inherits from each parent. Knowing your genotype is significant in determining your risk for the deficiency and the risk of your children. (For more on Alpha-1 genotypes, see ‘What will I learn from the ACT test?’ below.)
Why is the ACT study free?
Participation in the ACT study is free because we use the responses you provide in the questionnaire for our research.
How is my information kept confidential?
Your privacy as an ACT participant is protected to the extent permitted by law. Each ACT participant is assigned a unique alpha-numeric code when they consent to be in the study. This code is saved in our secure database and written on your blood card. When you return your sample to MUSC, the bottom half of the blood card with your name and date of birth is removed and locked in a secure location. The “coded” blood card is sent for testing to the Univ. of Florida. Results are sent to MUSC, matched with your unique code, and mailed to your home. Your personal information and ACT results are not shared with your doctor’s office or insurance company. We also do not rent or sell our address or email list.
What is the purpose of the questionnaire?
The questionnaire data is used for Alpha-1 research. This questionnaire inquires about your thoughts and feelings associated with learning genetic information. It also touches on the relationship between genes and different diseases as well as lifestyle choices. Remember: Your personal information is not shared with anyone.
How can I obtain a free ACT kit?
You can call our toll free number at 877-886-2383 or email us at alphaone@musc.edu to request a testing kit. We will give you the preliminary instructions on how to receive your kit including our web address, signing our electronic informed consent, and completing our electronic research questionnaire. Your kit will be mailed once the online informed consent is signed and the research questionnaire is completed correctly.
How long does the testing process take?
After the online forms are completed, the finger stick kit is mailed within 2 weeks. When the blood sample is returned, the results are sent by US mail in 3-4 weeks.
What will I learn from the ACT test?
ACT testing determines the genotype and the estimated Alpha-1 antitrypsin (AAT) level. The genotype refers to the pair of genes you inherited from each parent. These two genes tell you whether you are deficient or not with Alpha-1 or if you are a carrier of Alpha-1.

For example, if your results return showing an MZ genotype, you are a carrier because you inherited one normal copy (M) and one abnormal copy (Z). You do not have Alpha-1; you are a carrier. Your MZ genotype will produce reduced amounts of AAT but should provide enough to protect you from symptoms, unless you smoke. As a carrier of Alpha-1, you will pass either the M or the Z to your children. The only way to find out which gene they received from you is to test them.
What should I do after I get my results?
You can contact your physician or primary healthcare provider. Depending on the risk, your doctor can create a health plan including an exercise and nutrition program. He/she can also lower the risk of lung disease by assessing your health behavior (smoking, alcohol use and excess weight).

If you are diagnosed as deficient for Alpha-1 or a carrier, you can contact the resources listed in the brochures which are provided with your result letter.

You should avoid risk factors such as smoking, secondhand smoke, dust, harmful fumes and excessive alcohol use.

You should get regular vaccinations to protect against bacteria infections from pneumococcal pneumonia and Haemophilus influenza.  An annual influenza vaccine is highly recommended. 

You can also inform your family members and urge them to test for Alpha-1.
Can I just call to get a test kit without going online for the consent and questionnaire (skip online process)?
No. Since ACT is a research study, we have a protocol we must follow. Therefore, we need your signed consent and questionnaire responses for our research.
Can I order a test for my spouse?
Yes, you can order a test for your spouse as long as he/she fills out the questionnaire him/herself and signs his/her own consent.
Can I order a test for my minor children?
Yes, you can order a test for your minor child/ren (aged 17 and below). We encourage those aged 12 to 17 to fill out their own questionnaires with their parent’s assistance. The parent must sign the consent giving their child/ren permission to participate in ACT.
My son is 18 and attends college out of state. Can I order a testing kit for him?
No, he is an adult so he must decide for himself if, how, and when he wants to test.
Can I order a test for my sister?
No, you can only order a kit for yourself, your spouse and your minor child/ren (aged 17 and below). Everyone else must order their own kit, for example, a sibling, cousin, parent, grandparent, fiancé(e), friend, significant other and anyone aged 18 and above.
My grandmother needs to be tested but she lives in Israel. Can I order a kit for her?
No. The ACT Study tests people in the US, Puerto Rico, Canada, and other US territories only.
What is your research for?
Research in Alpha-1 antitrypsin deficiency is needed in order to better understand the disease and to understand what causes emphysema and/or liver disease in only some people with the condition. It is also needed to improve current treatments. The blood samples you provide are kept at the University of Florida’s Genetics Lab to assist their team of scientists in these efforts. If you are interested in participating in more research on Alpha-1 and your results from the ACT study identify you as an MZ carrier or as Alpha-1 deficient, you will be invited to join our Alpha-1 Research Registry. This is a free and confidential database established to facilitate research and promote development of improved treatment and a cure for Alpha-1. Becoming a member of the Registry provides you the opportunity to participate in clinical trials of new therapeutic approaches in addition to other Alpha-1 research studies.
What if AAT levels are outside the normal range for a given genotype?
AAT is an acute phase reactant protein. The levels of AAT are elevated in acute and chronic inflammatory conditions such as trauma, pregnancy, oral contraceptives and stress. For example, if you had your test performed when you had a fever, the levels may return elevated.

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Genetic Counseling FAQs

What is Alpha-1 Antitrypsin Deficiency?
Alpha-1 antitrypsin deficiency (more simply called Alpha-1) is an inherited condition that causes lower levels of Alpha-1 antitrypsin in the blood. People with Alpha-1 have an increased risk to develop lung disease. Risk for liver disease is also increased in many people with Alpha-1. Lung disease typically occurs in adulthood, while liver disease can occur in children or adults.

Alpha-1 antitrypsin is a protein that is mostly made in the liver. It is then secreted into the blood. Alpha-1 antitrypsin is needed in circulation to protect the lungs. Without enough of it, the lungs are at increased risk to develop chronic obstructive pulmonary disease (COPD). The way each person's body produces Alpha-1 is genetically determined. Everyone inherits one copy of the Alpha-1 gene from each parent, for a total of two copies.

Abnormal Alpha-1 genes result in deficiency. The Z allele is a common mutation that instructs the liver to make abnormal Alpha-1 protein. The abnormal protein builds up in the liver, rather than passing into circulation. People with two Z genes are at significantly increased lifetime risk for lung and liver disease.  
Not everyone who inherits Alpha-1 will develop symptoms, or the same symptoms. It can be important to know about Alpha-1 because risks to get sick can be reduced and better medical care can be provided for people with symptoms. For people with Alpha-1 related lung disease a specific therapy, called augmentation therapy, may be recommended. Additionally, because Alpha-1 genes run in families, knowing about Alpha-1 can be important for relatives and family planning.
What are genes?
Genes are units of DNA. People have about 20,000 genes. Our genes are packaged on our chromosomes, which are found inside the nucleus of our cells. Genes are transmitted from parent to child. People get one copy of each gene from their mother and one from their father (sex chromosomes excluded).

Genes tell our bodies how to produce proteins that are necessary for normal human function. Genes are the biological blueprint for how we grow, function and develop. Everyone has changes in their genes that make them unique. Changes in genes can be benign variants (neutral) or cause problems. Changes that result in disease or higher risks are called mutations. Mutations in one specific gene, called SERPINA1, result in Alpha-1.
What are alleles?
Alleles are different versions of the same gene. The normal Alpha-1 allele is called “M”. Abnormal alleles, also called deficiency alleles, occur due to mutations in the DNA of the Alpha-1 gene. The most common deficiency alleles are “S” and “Z.” There are also more than 100 other rarer deficiency alleles. The M allele produces normal Alpha-1 protein (normal quantity and normal function). Deficiency alleles produce abnormal Alpha-1 protein, and/or not enough Alpha-1 protein. Different deficiency alleles have different effects on Alpha-1 level and function, thus different allele combinations (genotypes) lead to different disease risks.
What are genotypes?
A genotype is the combination of Alpha-1 alleles you have. It is represented by 2 letters since everyone has 2 Alpha-1 alleles. The normal genotype is MM. Carrier genotypes include MS and MZ. Deficiency genotypes include ZZ and SZ. There are many more rare Alpha-1 genotypes. Contact the genetic counselor if you have questions about finding out your genotype or what your genotype means.
What is Genetic Counseling?
Genetic counseling is the process of helping people understand and adapt to the medical, psychological and familial implications of genetic contributions to disease. This process integrates:

  • Interpretation of family and medical histories to assess the chance of disease occurrence or recurrence.
  • Education about inheritance, testing, management, prevention, resources and research.
  • Counseling to promote informed choices and adaptation to the risk or condition.

See www.nsgc.org for more information about genetic counseling or to find a genetic counselor near you.
How does Alpha-1 run in families?
Everyone has two copies of the Alpha-1 gene. Severe Alpha-1 antitrypsin deficiency occurs when both copies of a person’s Alpha-1 genes do not work normally due to mutations in the DNA. Genes are inherited and we get one copy of the Alpha-1 gene from our mother and the other from our father. Likewise, if you have children, you pass on one of your two Alpha-1 genes, and the child gets their second Alpha-1 gene from the other parent. When both parents have one or more abnormal Alpha-1 genes there is a risk to have a child with severe deficiency.
What does it mean to be a carrier?
Alpha-1 carriers are people who have one normal Alpha-1 gene (called M) and one abnormal Alpha-1 gene (most commonly S or Z). Carrier genotypes include MS, MZ, M-Other. Carriers may be termed “mildly deficient” because this combination of genes leads to a lower Alpha-1 level than expected for most people with two normal genes (MM) but higher than that of someone with severe deficiency caused by two abnormal genes (ZZ, SZ).

Most carriers do not develop Alpha-1 related symptoms; however, recent research has shown that carriers who smoke are at high risk for lung disease. Some carriers may also have a small increased risk for liver disease. Carriers should avoid smoking and live a healthy lifestyle.

Carriers have a 50% chance of passing on their abnormal Alpha-1 gene to each child. Thus, any child of a carrier has a 50% chance to be a carrier, too. If two carriers have children together, there is a risk to have a child with severe Alpha-1 antitrypsin deficiency. This happens when the child inherits an abnormal gene from both the mother and the father.
Genetic chart
What is a Pi type?
Pi stands for Protease Inhibitor. Alpha-1 antitrypsin is a type of protein called a protease inhibitor, so Pi type is the type(s) of Alpha-1 protein produced by your body (primarily in your liver). A Pi type is also represented by two letters (e.g. MM, MZ, MS, ZZ). In most cases your Pi type and your genotype are the same. Contact the genetic counselor if you have questions about your Pi type.
Who should be tested?
According to the 2003 ATS/ERS Guidelines, testing is recommended for:

  • Full siblings of adults with Alpha-1
  • Any adult with COPD, emphysema, or incompletely reversible asthma
  • Asymptomatic adults with persistent obstruction and risk factors
  • Adults with necrotizing panniculitis
  • Anyone with unexplained liver disease

According to the 2003 ATS/ERS Guidelines, testing should be considered for:

  • Parent, child or more distant relative of someone with one or more abnormal Alpha-1 genes
  • Partner of Alpha-1 affected or carrier
  • People with a family history of COPD or liver disease not known to be Alpha-1 related
  • Adolescents with persistent airflow obstruction
  • Symptomatic adults in countries with lower Alpha-1 incidence

Call the genetic counselor if you have questions or concerns about whether to have Alpha-1 testing. Decisions can be made in the context of your personal and family history, as well as your unique situation and goals.
How can I be tested?
There are several options for getting tested. The Alpha-1 Coded Testing Study is a free and confidential testing program supported by the Alpha-1 Foundation. Testing through this program is voluntary and nobody gets your results except you. You will receive your results in the mail. The genetic counselor is available to help you understand your results.

You may also ask your healthcare provider to order testing for Alpha-1. Many labs offer Alpha-1 testing. Ask your healthcare provider if you have questions about which test is being ordered and details of the test. If your healthcare provider orders your test, the results will go to that healthcare provider to be shared with you. You can still call the genetic counselor to discuss your results further.
What does testing involve?
Alpha-1 testing requires a blood sample, usually dried blood spots. These can be obtained by a finger stick using a lancet. Alternatively, a blood draw may be performed in a doctor’s office to test for Alpha-1.

Only a blood test can diagnose or rule out Alpha-1.
What does the lab do to test for Alpha-1?
It depends on the lab. There are several methods of testing for Alpha-1 and some labs use more than one to ensure accuracy.

An immunoassay, also called a ‘level’, measures the quantity of Alpha-1 in your blood. This is done on one of two scales, either uM or mg/dL, and is reported as a number. This is helpful to see if you have low level that indicates deficiency.

Phenotyping looks at the Alpha-1 protein(s) in your blood using a technique called isoelectric focusing. The results are two letters called a Pi type.*

Genotyping looks at the Alpha-1 gene for common gene mutations. The results are two letters called a genotype.*

    *Genotyping and phenotyping give you the same result in most cases.

Gene sequencing spells out the DNA sequence of the Alpha-1 gene. This is useful for clarification of less common Alpha-1 gene mutations.
What does my genotype mean?
MM: This is the normal Alpha-1 genotype. About 94% of Caucasians are genotype MM. MM individuals have no increased risk for Alpha-1 related disorders and no increased risk to relatives. MM individuals will pass an M to any child they have. The child’s other Alpha-1 gene comes from the other parent.

MZ, MS, M-Other: You are a carrier of Alpha-1 and likely have a mild deficiency. See the Carrier section above. All of your first degree relatives (parents, children, and full siblings) have a 50% risk to be carriers based on your genotype. Testing should be considered for these family members. Based on family history, some individuals in your family may have an increased risk for severe Alpha-1 deficiency. Call the genetic counselor to discuss your unique situation.

SS: This genotype is associated with an intermediate Alpha-1 level. Risks for lung disease may be mildly increased and smoking should be avoided. Risks for liver disease are not increased.

SZ: This genotype causes a moderate to severe deficiency and an increased risk for Alpha-1 related lung disease. Liver disease is less common. Your specific risks and symptoms should always be discussed with a trained medical professional. See http://alpha-1foundation.org/clinical-resource-centers/ to find an Alpha Doc near you. Call the genetic counselor for more information.

Your parents and children are “obligate carriers” of either the S or the Z. Carriers may wish to know this for lifestyle planning, healthcare management and reproductive decision making. Testing should be considered. Risk for a given individual to be more severely affected depends on the genotypes of both of their parents. It uncommon for multiple generations of a family to be severely affected (SZ, ZZ), though rarely this can occur.

Your full siblings are at-risk to have the SZ genotype, as well. They may also be Alpha-1 carriers or unaffected and not a carrier. Testing is recommended.

ZZ: This genotype causes a severe deficiency and significantly increased risk for Alpha-1 related lung disease in adults. Risk for liver disease is also increased in infants and adults. Severe liver disease affects a small portion of infants with the ZZ genotype. Your specific risks and symptoms should always be discussed with a trained medical professional. See http://alpha-1foundation.org/clinical-resource-centers/ to find an Alpha Doc near you. Call the genetic counselor for more information.

Your parents and children are “obligate carriers” of the Z allele. Carriers may wish to know this for lifestyle planning, healthcare management and reproductive decision making. Testing should be considered. Risk for a given individual to be more severely affected depends on the genotypes of both of their parents. It uncommon for multiple generations of a family to be severely affected (SZ, ZZ), though rarely this can occur.

Your full siblings are at-risk to have the ZZ genotype, as well. They may also be Alpha-1 carriers or unaffected and not a carrier. Testing is recommended.
I am a healthcare provider and ordered Alpha-1 testing for a patient. How can I get the results?
The Alpha-1 genetic counselor is available to interpret and discuss Alpha-1 results after you have them, but is not able to obtain clinical test results for any medical office. In order to obtain results, or check on the time frame for results availability, you should contact the lab that performs testing for your office.
I sent in my blood for ACT testing. When can I expect my results?
Results are delivered to you by mail approximately 4 weeks after you submit your blood sample for testing.

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