Alpha-1 Anti-trypsin Deficiency: What is it and how is it treated?Lawrence Martin, M.D., FACP, FCCP
Clinical Professor of Medicine
|
Phenotype - risk for emphysema |
True plasma level (μmol/L) |
|
MM - No increase in risk MZ - Possible mild increase SS - No increase SZ - Mild increase ZZ - High risk (80-100%) Null/Null - High risk (100% by age 30) |
20 - 53 12 - 35 15 - 33 8 - 19 2.5 0 |
These risks pertain to emphysema, but cirrhosis may also occur, due to α-1 AT accumulation in the liver. However, in a subgroup of patients who are "null" there won't be any liver disease, since no α-1 AT is made.
Probably most people who have α-1 AT deficiency don't know about it, because they don't smoke and are not sick. The estimated prevalence ranges from 1 in every 3000 to 1 in every 5000 people. At present it's estimated that less than 6% of severely deficient people are currently identified.
It depends on 1) How severe it is and 2) Your smoking history.
Three out of 4 adults with severe α-1 AT deficiency will get emphysema, sometimes before age 40. SMOKERS WITH α-1 AT DEFICIENCY ARE AT MUCH GREATER RISK OF DEVELOPING EMPHYSEMA. Children with α-1 AT deficiency can develop liver problems that last their whole lives.
Cigarette smoke is harmful not only because it directly affects the lungs (it's the major cause of emphysema without α-1 AT deficiency), but it also decreases the activity of α-1 AT. Cigarette smoking accelerates the onset of symptomatic disease by approximately 10 years.
An estimated 1-3% of patients with diagnosed COPD (chronic obstructive pulmonary disease), which encompasses both emphysema and chronic bronchitis, have α-1 AT deficiency. Symptoms include progressive shortness of breath, cough, sputum production and/or wheezing.
A simple blood test can tell if you have the deficiency. Most hospital laboratories report serum α-1 AT levels in milligrams per decimeter (mg/dl), with a reference range of approximately 100-300 mg/dL; these levels overestimate the true level, which is given in umol/L, by 35-40%. Generally a conversion factor will be available to convert the mg/dl value into umol/L.
For example, the lab reports α-1 AT is 100 mg/dl and the conversion factor is x .185, the "true value" is 18.5 umol/L, which is slightly low (see table above). Since the value is reduced, the lab should also perform an analysis of the phenotype.
If you have α-1 AT deficiency, your family members should also take the blood test. Brothers and sisters of someone with α-1 AT deficiency have a 1 in 4 chance of inheriting the genes that cause α-1 AT deficiency. Children of a parent with α-1 AT deficiency should also be tested.
There is no cure, but there is treatment to slow down the disease process.
First, if you smoke you MUST stop. Smoking accelerates the disease. Second, if you have lung disease you should be receiving appropriate treatment, same as if you didn't have α-1 AT deficiency.
Specific treatment is with an intravenous infusion of Alpha-1-Proteinase Inhibitor (Human). This replacement therapy for the α-1 AT deficiency is a protein that comes from donated human plasma. It is not recommended for α-1 AT deficiency UNLESS the patient has symptomatic and/or progressive emphysema. Replacement therapy is not appropriate for liver disease patients; if liver disease is severe, transplantation may be needed. Replacement therapy is also not recommended in pediatric patients. There are three manufacturers of alpha-1 protease, with brand names Prolastin, Aralast and Zemaira.
Prolastin, The manufacturer Talecris states on their web site:
"Alpha1-Proteinase Inhibitor (Human) is indicated for chronic replacement therapy of individuals having congenital deficiency of alphα-1 PI (alpha1-antitrypsin deficiency) with clinically demonstrable panacinar emphysema. Weekly Prolastin therapy has demonstrated a low occurrence of side effects. In clinical studies with Prolastin, reactions were observed in 1.16% of infusions, the most common events being fever (0.77%), light-headedness (0.19%), and dizziness (0.19%). As with all plasma-derived therapeutics, the potential to transmit infectious agents cannot be totally eliminated. Individuals with selective IgA deficiencies who have known antibody against IgA (anti-IgA antibody) should not receive Prolastin, since these patients may experience severe reactions, including anaphylaxis, to IgA which may be present."Aralast. The manufacturer Baxter states on their web site:
"ARALAST is indicated for chronic augmentation therapy in patients having congenital deficiency of A1-PI with clinically evident emphysema. ARALAST is not indicated as therapy for lung disease patients in whom congenital A1-PI deficiency has not been established. Important Safety Information. ARALAST is contraindicated in individuals with selective IgA deficiencies (IgA level less than 15mg/dL) who have known antibody against IgA, since they may experience severe reactions, including a severe, potentially life-threatening allergic reaction to IgA, which may be present. ARALAST is made from human plasma. It may carry a risk of transmitting infectious agents, e.g. viruses, and theoretically, the Creutzfeldt-Jakob disease (CJD) agent. The most common symptoms during the clinical study were headache (0.3%) and sleepiness (0.3%). Post market adverse event data have indicated reports of infusion site pain associated with the administration of ARALAST."Zemaira. The manufacturer CSL Behring states on their web site:
"Zemaira is indicated for chronic augmentation and maintenance therapy for adults with alpha1-proteinase inhibitor (A1-PI) deficiency and emphysema. Clinical data demonstrating the long-term effects of chronic augmentation therapy with Zemaira are not available. As with other Alphα-1 therapies, Zemaira may not be appropriate for the following adult individuals as they may experience severe reactions, including anaphylaxis: individuals with a known hypersensitivity and/or history of anaphylaxis or severe systemic reaction to A1-PI products or their components and individuals with selective IgA deficiencies who have known antibodies against IgA. In clinical studies, the following treatment-related adverse reactions were reported in 1% of subjects: asthenia (fatigue), injection-site pain, dizziness, headache, paresthesia (tingling), and pruritus (itching). Zemaira is derived from human plasma. As with all plasma-derived products, the risk of transmission of infectious agents, including viruses and, theoretically, the Creutzfeldt-Jakob disease (CJD) agent, cannot be completely eliminated."Finally, in the most severe cases lung transplantation may be considered.
If a patient is diagnosed with unequivocal alpha-1 antitrypsin deficiency AND disease resulting from that deficiency, he or she may be referred for once-a-week replacement infusions. treatment may be given in any medical office equipped for IV infusions (such as an outpatient cancer center), in a hospital or in the patient's home. There is a national network of nurses certified in alpha-1-care.
More than 100 phenotypic variants of α-1 AT deficiency have been identified, but phenotype ZZ is responsible for nearly all cases of α-1 AT deficiency emphysema and liver disease (see table, above). ZZ phenotype serum levels range from 2.5-7 μmol/L, about 10-20% of the reference range levels. Other phenotypes associated with α-1 AT emphysema and liver disease include SZ and Z/Null. Null/Null is not associated with liver disease but is associated with α-1 AT deficiency emphysema.
It's not a routine test, premarital or otherwise, and will likely not be covered by insurance. However, if there is history of α-1 AT deficiency in your nuclear family and you are planning on having children, you could discuss testing with your physician. Be aware that most physicians are not knowledgeable about this condition (one reason being that it's not a routine test), so any abnormal result will raise a lot more questions and likely require specialty referral.