Alpha 1 -Antitrypsin Deficiency

One of the most common inherited disorders (1 in 2500 in case of European ancestry; uncommon in Asians)

Less than 10% of individuals with AAT deficiency are currently identified.

AAT deficiency is the most common genetic cause of liver disease in neonates and children.

About 1% to 5% of pts with COPD have AAT deficiency.

Approximately 15% of adults with AAT deficiency develop liver cirrhosis.

Dynamic hyperinflation (air-trapping or auto-PEEP) with positive pressure ventilation, leading to hypotension and CV collapse

Resp failure

Hepatic impairment

Poor wound healing (panniculitis)

Missed or incorrect (e.g., asthma) diagnosis

Liver cirrhosis

Glomerulonephritis and nephrotic syndrome

Gastrointestinal complications incl ascites

Panniculitis

Vascular disease

AAT is secreted in the liver as the most abundant of the serine protease inhibitors (serpins), with over 100 genetic variants of AAT identified.

Panacinar pulm emphysema is the most common manifestation, and is the major cause of disability and death.

Most commonly presents with slowly progressive dyspnea in mid-life, typically 2 to 3 decades earlier than do smokers with emphysema and normal AAT levels.

Some pts present with otherwise unexplained hepatic dysfunction.

Cigarette smoking greatly accelerates the progression of emphysema in AAT deficiency.

AAT deficiency may present early after birth as neonatal jaundice and hepatitis, in infancy as cholestatic jaundice, or in children as liver cirrhosis or failure.

AAT deficiency is the most common condition requiring liver transplantation in children.