Saturday, April 7, 2012

Alpha-1 antitrypsin deficiency: a clinically under-recognized inherited disorder

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.
Risk factors:
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 ┬Ámol /L. Population studies suggest a protective threshold of 11 ┬Ámol 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.

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.

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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