nemoci-sympt/PLICNI/alfa-1-antitrypsinova-deficience/popis-epidemiologie

Synonyma

• Alpha-1 antitrypsin deficiency
• A1AD
• AATD

Definice

• Under-recognized genetic disorder due to mutations in the SERPINA1 gene

• Defective production of alpha-1 antitrypsin protein - AAT
• Decreased AAT activity in the blood and lung
• Deposition of excessive abnormal AAT protein in the liver
• Neutrophil elastase destroys alveoli
• Causes lung disease [1]
• Abnormal AAT can also accumulate in the liver
• Cause damage to this organ [1]
• Emphysema in AAT deficiency is considered due to an imbalance between
• Neutrophil elastase in the lung
• Destroys elastin
• Elastase inhibitor AAT
• Protects against proteolytic degradation of elastin
• “toxic loss of function” [1]

Historie

• First described in the 1960s [2]
• By Carl-Bertil Laurell (1919–2001), at the University of Lund in Sweden
• Laurell + medical resident, Sten Eriksson, made the discovery
• Absence of the ?1 band on protein electrophoresis in five of 1500 samples
• 3/5 patient samples were found to have developed emphysema at a young age
• Liver disease was made six years later
• Harvey Sharp et al. described A1AD in the context of liver disease [2]

Epidemiologie

Wordwide

• Estimated that worldwide
• More than 3 million people
• Allele combinations associated with severe deficiency of AAT [1]
• 161 million people have
• MS or MZ [1]
• Affecting 1 per 3000-5000 individuals [4]
• Severe AATD affects an estimated 70,000-100,000 individuals [4]
• Approximately 25 million people carry of at least 1 deficient gene [4]
• Less than 10% of severely deficient individuals are currently identified [4]
• Estimated 117 million carriers [4]
• Estimated 3.4 million affected individuals [4]
• Identified in all populations

Evropa

• Most common in individuals of Northern European (1 in 1600) and Iberian descent [4]
• Similar rates among white persons worldwide [4]
• Affects about 1 in 1500 - 3500 individuals with European ancestry [1]
• Affects about 1 in 2500 people of Europeans descent [2]
• Severe deficiency
• In about 1 in 5,000 [2]

Asie

• Uncommon in people of Asian descent [1] [2]

USA

• Considered to be rare
• Estimates that 80,000 - 100,000 individuals in the United States have a severe deficiency of AAT
• Disease is under-recognized
• Z allele - 2-3% of the Caucasian population in the United States [3]

Race

• White persons constitute
• Estimated 117 million carriers
• 3.4 million affected individuals
• Other than whites are affected less frequently [4]

Sex

• Women and men are affected in equal numbers.

Prognóza

• People with AAT deficiency usually develop
• The 1st signs and symptoms of lung disease between ages 20 and 50
• Rate of decline in lung function is strongly dependent on cigarette smoking [1]