Dear Respiratory Friends, we are happy to present new post from Doctor Marilia Varella (Brazil) abot Alpha-1 antitrypsin deficiency!
What is Alpha-1 antitrypsin
deficiency?
It
is a clinically under-recognized inherited disorder affecting the lung
(emphysema), liver (neonatal hepatitis, chronic liver
disease),
and rarely, skin (panniculitis). Emphysema is thought to
result from an imbalance between neutrophil elastase in the lung and the
elastase inhibitor AAT, which protects against proteolytic degradation of
elastin.
The
prevalence of AAT varies considerably from one country to another; however, it
is estimated that more than 3 million people worldwide have allele combinations
associated with severe AAT deficiency.
Recent
surveys demonstrated that there is an average delay of 7.2 years between the
first onset of symptoms and the diagnosis even in individuals with severe
deficiency; those individuals also reported seeing at least three (up to ten) clinicians
before the diagnosis of AAT deficiency was first made.
It`s
also important to notice that under-recognition persists despite extensive
educational efforts and the publication of evidence-based guidelines for
diagnosis and management of AAT deficiency.
AAT
(encoded by the gene PI, MIM +107400) is a member of the serpin family of
protease inhibitors. The normal alpha-1 antitrypsin allele is the M allele.
Over 100 allelic variants have been described, of which the most common
severely deficient variant is the Z allele.
The
normal plasma concentration of AAT ranges from 20 to 48 µmol /L. Population
studies suggest a protective threshold of 11 µmol per L, below which there is
insufficient AAT to protect the lung.
Severe
deficiency of AAT poses a strong risk factor for early-onset emphysema, but not
every severely deficient individual is destined to develop emphysema. Smoking is the major factor influencing the course of COPD.
Symptoms:
The clinical manifestations
of AAT deficiency during the first two to three decades of life is that of
liver disease, specifically chronic elevation of liver enzymes or cirrhosis.
Beyond the first two to
three decades of life, patients with severe deficiency of AAT have an accelerated
rate of lung function decline.
The clinical presentation
of emphysema due to AAT deficiency has many features in common with usual COPD.
However, the onset of emphysema in AAT-deficient individuals may be earlier
than that in non-AAT-deficient individuals, who usually present in the sixth
and seventh decades of life.
Emphysema associated with
AAT deficiency often shows a characteristic chest radiographic pattern, in
which bullous changes are more prominent at the lung bases than at the apices.
Diagnosis:
Patients
with persistent airflow obstruction on spirometry should be tested. Additional
features that should lead clinicians to test for severe AAT deficiency include:
·
Emphysema in a young
individual (≤45 years)
·
Emphysema in a nonsmoker or
minimal smoker
·
Emphysema characterized by
predominant basilar changes on the X-Ray
·
A family history of
emphysema and/or liver disease
·
Clinical findings or
history of panniculitis
·
Clinical findings or
history of unexplained chronic liver disease
The diagnosis of severe AAT
deficiency is confirmed by demonstrating a serum level below 11 micromol/L in
combination with confirmation of a severe deficient genotype (generally
determined by isoelectric focusing or polymerase chain reaction testing).
Browse through the links
listed below to learn more about AAT deficiency:
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