Alpha-1-antitrypsin deficiency
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Alpha-1-antitrypsin is a protease inhibitor, deficiency of which is associated with
emphysema and liver disease. In most cases the disease is not severe and only rarely
leads to liver failure.
Deficiency of alpha-1-antitrypsin activity is associated with several of the electrophoretic
variants of serum alpha-1-antitrypsin. The normal enzyme variant is called M. The
variants that are associated with marked emphysema and liver disease are called
S and Z. The Z type is the least common, but a child who carries two alleles/genes
of this type is at risk to have the most severe form of the disease.
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Inheritance pattern
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Autosomal
recessive.
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Penetrance
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Incomplete.
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Associated features that can be demonstrated in tests performed during pregnancy
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There are no specific ultrasound signs or associated defects.
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What is the risk of recurrence in a subsequent pregnancy?
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For a couple who has already had an affected child, the risk is 25% in every subsequent
pregnancy.
This also applies to a couple where both partners have been found to carry the Z
(or S) allele.
When only one parent carries the Z allele (or S allele), there is no risk that any
of their offspring will have the disease.
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Molecular genetic information
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Gene, Location
The protein is encoded by a gene, PI, that is located on the distal long arm of
chromosome 14q31-32.
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Genetic testing
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Diagnostic testing
A direct test can be performed to identify the abnormal variants Z and S at the
DNA level. See:
Testing the disease-causing gene for mutations that are common in a specific ethnic
group - autosomal recessive diseases.
Carrier testing
All ethnic groups are similarly affected. The carrier frequency in the healthy Jewish
population is 1:80. Two major variant forms, Z and S, are associated with Alpha-1-antitrypsin
deficiency, and both can be tested relatively easily.
Due to the relatively rarity of this disease and especially since most cases are
treatable adult diseases, general population screening is not justified.
See also: "Introduction to population DNA screening
for autosomal recessive diseases such as Cystic fibrosis and others".
Fetal testing
There is usually no indication to test the fetus for this disease.
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