Alpha-1 antitrypsin deficiency hidden in allegedly normal variants

Area of Science:

• Genetics
• Pulmonology
• Biochemistry

Background:

• Alpha-1 antitrypsin deficiency (AATD) is a genetic disorder.
• Rare variants, such as Mmalton, are less understood than common PI*S and PI*Z alleles.
• The Canary Islands have shown a higher prevalence of Mmalton alleles.

Purpose of the Study:

• To investigate the distribution of Mmalton mutations in the Canary Islands.
• To assess the clinical and biochemical profile of Mmalton carriers in a specific population.

Main Methods:

• A cross-sectional study of 648 allergic asthma patients.
• Real-time PCR was used to assay the Mmalton mutation in the SERPINA1 gene.

Main Results:

• Three patients (0.46%) were identified as Mmalton allele carriers.
• All carriers exhibited low Alpha-1 antitrypsin (AAT) levels (53.9–90 mg/dL).
• Despite low AAT levels, carriers were asymptomatic with normal lung function and liver enzyme levels.

Conclusions:

• While PI*S and PI*Z are the most common AATD genotypes, rare variants like Mmalton should be considered, especially with low AAT serum levels.
• The Mmalton mutation, typically associated with varied clinical presentations, resulted in asymptomatic individuals in this study.
• This study underscores the need for comprehensive genetic screening for AATD, including rare variants, in relevant populations.