ALPHA -1 ANTITRYPSIN DEFICIENCY
Last Updated : 3/8/2010
Ira Shah
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What is

alpha - l-antitrypsin

?

Alpha -1- antitrypsin is a glycoprotein produced by the liver. Its primary function is to protect the lungs from neutrophil elastase, which is an enzyme that digests the phagocyte cells and bacteria to promote healing. However, it requires alpha-l - antitrypsin to prevent it from damaging the lung tissue.Alpha-l- antitrypsin is an acute- phase reactant. Its level increases to 3 or 4 times the normal amount at times of infection, pregnancy or any conditions that cause an increase in neutrophil elastase.

What happens where there is

deficiency of alpha-l- antitrypsin

?

In alpha -l deficient persons there is insufficient amount of alpha-1 antitrypsin circulating in the blood, hence the destructive effect of neutrophil elastase goes unchecked and lung tissue is destroyed causing emphysema, asthma, chronic bronchitis and repeated chest infections.In some patients, alpha -1- antitrypsin may be produced normally, however the liver may not secrete the protein into the blood. Such patients may also have cirrhosis of the liver. This is seen in 12-15 % of the patients especially children. Very rarely they may suffer from a condition called panniculitis due to destructive action of unrestrained neutrophils.

How does alpha-1 antitrypsin deficiency occur?
It is a genetic disorder and is inherited as an autosomal recessive condition. The normal phenotype is PiMM. When both parents contain the abnormal gene (Piz) and pass it on to their offspring, it results in a phenotype of PiZZ, which leads of emphysema. Although, there are various alleles of the gene and several phenotypes, the phenotypes associated with emphysema are PiSZ, PiZZ and PiNull. The Null gene is one that produces no detectable level of alpha -1 antitrypsin. Patients with Null-Null phenotype are at increased risk for developing emphysema, yet do not suffer liver damage greatly.

How does alpha-1 antitrypsin deficiency occur?
There are two primary theories proposed:
External attack Theory: As there is lack of alpha-1-antitrypsin in the blood, the liver is subject to attacks by neutrophil elastase, other destructive enzymes or bacteria.
Internal attack Theory - Alpha-1 antitrypsin is produced normally, however is not secreted in circulation. The alpha-1 antitrypsin that accumulates in the liver cell membrane may cause the destruction of the liver. This theory is the most widely accepted theory. Around 10% of alpha-1 antitrypsin deficient infants develop cirrhosis in childhood. Of the remainder about 10% develop cirrhosis later. Cirrhosis is commonest in PiZZ phenotype and is almost not seen in Pi Null phenotype.



Contributor Information and Disclosures

Ira Shah
Consultant Pediatrician, B.J.Wadia Hospital for Children, Mumbai, India


First Created : 3/5/2001

References

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