Alpha-1-antitrypsin phenotyping
Alpha-1-antitrypsin phenotyping-13513
Alpha1 Antitrypsin Phenotyping
Pi Phenotype
Protease Inhibitors
Phenotype
Definitive analysis of hereditary alpha1-antitrypsin deficiency, which is associated with chronic obstructive pulmonary disease (COPD) (panacinar emphysema), hepatic cirrhosis, and hepatoma. Cholestasis with neonatal hepatitis is found in a minority of neonates with A1 AT deficiency.
Overnight fasting is preferred
Immediatley following collection, mix sample by gently inverting 5 times
- Allow sample to clot for a minimum of 30 minutes
- Spin within two (2) hours of sample collection
Gold serum separator (SST) tube
- Allow sample to clot
- Spin
- Transfer serum to a Transfer vial/tube with cap - 12mL (LabCorp) within two (2) hours of sample collection
Ambient (preferred) - 21 days
Refrigerated - 21 days
Frozen - 21 days
Freeze/thaw cycles: Stable x2
Phenotype: isoelectric focusing (IEF)
Total: immunologic
| Phenotype | Population Incidence | a1AT Concentration (mg/dL) |
| MM | 86.50% | 96−189 |
| MS | 8.00% | 83−161 |
| MZ | 3.90% | 60−111 |
| FM | 0.40% | 93−191 |
| SZ | 0.30% | 42−75 |
| SS | 0.10% | 62−119 |
| ZZ | 0.05% | 16−38 |
| FS | 0.05% | 70−128 |
| FZ | Unknown | 44−88 |
| FF | Unknown | Unknown |
Most pathologic is homozygous state ZZ. An M null genotype will have phenotype as MM, but low serum level of α1AT. α1-antitrypsin deficiency may eventuate in or be associated with cholestatic hepatopathy in infants, a chronic hepatitis, familial infantile cirrhosis, or familial emphysema.1,2 The risks of cirrhosis and development of hepatoma are greater in males.
α1-antitrypsin (α1AT) is a glycoprotein synthesized in the liver and is the main component of the alpha1 globulins. α1AT serves to counter the effects of several serine proteases, including elastase and trypsin. When α1AT is deficient, unopposed activity of these enzymes results in emphysema. The age of occurrence of emphysema varies with the type of deficiency, ZZ being most severe, SZ less severe, and SS least severe. It often varies with the personal habits of the individual, especially regarding smoking. Individuals with α1AT deficiency have PAS-positive diastase-negative granules accumulate in the periportal hepatocytes. Eventually, damage occurs to the liver resulting in cirrhosis. It is especially important to detect α1AT deficiency early as a replacement therapy is now available that has received favorable review in a recent NIH study. Although the long-term effects of this therapy are still unknown, it does have great potential to decrease the severity of emphysema.
α1AT is a positive acute phase protein because it rises whenever there is tissue injury, necrosis, inflammation, or infection. Therefore, patients with α1AT deficiency who suffer from bronchitis, pneumonia, or similar respiratory inflammation may have falsely normal levels during acute illness. After the acute phase of illness has passed, repeat determinations often reveal the “true” or “resting” α1AT level, which is indicative of the heterozygous phenotypic deficiency.
Therefore, use of high-resolution electrophoresis that would detect the slower electrophoretic migration of the Z and S variants is preferred over quantification of α1AT by nephelometry or turbidimetry as a preliminary test for this deficiency. Further, a high-resolution electrophoretic system will detect heterozygotes, which could lead to important family studies of potentially deficient first-degree relatives who may benefit from therapy.
Serum α1AT may be increased in patients during normal pregnancy, chronic pulmonary diseases, hereditary angioneurotic edema, gastric diseases, liver diseases, pancreatitis, diabetes, carcinomas, renal diseases, and rheumatic diseases, and it may be decreased in patients with severe protein loss or in improper storage of specimen.
More than 95% of subjects who are severely deficient are homozygous for the Z allele (PiZZ). PiZZ subjects who smoke have a shorter life expectancy than do nonsmoking PiZZ persons. Variation in severity of clinical manifestations is recognized; some subjects with deficiency do not have significant impairment, but development of airway disease is partly a function of age.
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