Clinical considerations in individuals with α₁-antitrypsin PI*SZ genotype

Area of Science:

• Genetics
• Pulmonology
• Hepatology

Background:

• Alpha-1 antitrypsin deficiency (AATD) is an underdiagnosed genetic disorder linked to lung and liver diseases.
• Current research primarily focuses on the severe PI*ZZ genotype, leaving the PI*SZ genotype less understood.
• The PI*SZ genotype may be more prevalent than previously recognized, necessitating further investigation.

Purpose of the Study:

• To review existing data on the PI*SZ genotype in AATD.
• To explore prevalence, diagnostic timelines, symptom development, and risk factors in PI*SZ individuals.
• To identify research gaps for optimizing the identification and management of PI*SZ patients.

Main Methods:

• Narrative review of available scientific literature.
• Analysis of genetic prevalence, diagnostic age, and symptom onset.
• Evaluation of factors influencing disease progression and treatment considerations.

Main Results:

• The PI*SZ genotype is potentially more common than identified, with unclear treatment protocols.
• Data on age of diagnosis, symptom development, and impact of smoking history in PI*SZ individuals are evaluated.
• The protective threshold for AAT therapy and liver disease risks in PI*SZ patients are explored.

Conclusions:

• There is a need for optimized identification and management strategies for individuals with the PI*SZ genotype.
• Further research is required to clarify the role and efficacy of AAT therapy in PI*SZ patients.
• Understanding the PI*SZ genotype is crucial for improving AATD patient care.