The Phenotypes of Alpha-1 Antitrypsin Deficiency

The Basics The History The Genetic Path The Symptoms The Phenotypes The Treatments The Testing

How is AATD diagnosed?

Alpha-1 antitrypsin deficiency (AATD) is diagnosed through testing of a blood sample, when a person is suspected of having AATD. For example, AATD may be suspected when a physical examination reveals a barrel-shaped chest, or, when listening to the chest with a stethoscope, wheezing, crackles or decreased breath sounds are heard.

Testing for AATD, using a blood sample from the individual, is simple, quick and highly accurate.. Three types of tests are usually done on the blood sample:

Alpha-1 genotyping, which examines a person's genes and determines their genotype.
Alpha-1 antitrypsin PI type of phenotype test, which determines the type of AAT protein that a person has.
Alpha-1 antitrypsin level test, which determines the amount of AAT in a person's blood.

Individuals who have symptoms that suggest AATD or who have a family history of AATD should consider being tested.(3)

Alpha-1 Phenotypes & Serum Levels
Phenotype	Frequency (in population) (2)	mg/dl (Commonly Quoted Levels)	uM* (True Levels)	Emphysema Risk
Pi*MM	90%	150-350	20-48	No increase
Pi*MZ	4%	90-210	17-33	No increase
Pi*SS	1.5%	100-200	15-33	No increase
Pi*SZ	.2%	75-120	8-16	Mild risk
Pi*ZZ	.02%	20-45	2.5-7	High risk
Null-Null	very rare	0	0	High risk

* µM result can be derived from mg/dl by multiplying mg by .1923

Threshold protective level concept based on epidemiologic assessment of AAT levels and the risk for the development of emphysema
* Serum levels given are measured using a typical commercial standard (mg/dl) and the purified standard (uM) used in the U.S. Registry. A level of less than 11 uM is associated with an increased risk for emphysema. (1)

Clinical Symptoms of Childhood
Liver Disease and Liver Test Abnormalities
Main Finding	Percent
* Clinical signs of neonatal liver disease	17%
* Healthy infants with abnormal liver tests at age 3 mo	52%
* Risk of liver cirrhosis before adolescence	3%

* Based on a study of 127 Pi*ZZ children identified in a Swedish Neonatal Screening Study (4)

References:
1. American Thoracic Society/Europeon Respiratory Society, "Standards for the diagnosis and management of individuals with Alpha-1 Antitrypsin Deficiecny", American Thoracic Society web site 2003 Feb <http://www.thoracic.org/adobe/statements/alpha1.pdf>
2. Huskey, Robert. "Alpha 1-antitrypsin deficiency." University of Virginia, 10 Nov 1998. 2 Jan 2003 <http://www.people.virginia.edu/~rjh9u/antitryp.html>
3. How is Alpha-1 Antitrypsin diagnosed? National Genome Research Institute web site 2007 Feb <http://www.genome.gov/19518992>
4. Sveger T. "Liver disease in alpha1-antitrypsin deficiency detected by screening of 200,000 infants". N Engl J Med 1976;294:1316–1321.