Alpha-1 antitrypsin deficiency hidden in allegedly normal variants

Abstract

Introduction

Rare variants of Alpha-1 antitrypsin (AAT) deficiency (AATD) have been described by the Spanish registry of patients with AATD. The great majority of these rare variants are Mmalton alleles and many recent case series of them have been identified in the Canary Islands. The objective of this study was to analyze the distribution of Mmalton mutations in a Canarian population previously studied for the most common deficient alleles, namely PI*S (S) and PI*Z (Z), with PI*M (M) being the normal variant.

Methods

A cross-sectional study of 648 patients with allergic asthma was carried out. Mmalton mutation of the SERPINA1 gene was assayed by real-time PCR.

Results

Of the 648 patients, 3 (0.46%) were carriers of a Mmalton allele. All of them had low levels of AAT (53.9 mg/dL, 90 mg/dL, and 61 mg/dL, respectively) and were asymptomatic, showing normal lung function, radiological images, and levels of hepatic transaminases.

Conclusion

In conclusion, although the most frequent AATD genotypes are Z and S alleles, it is important to consider other rare variants, particularly when low AAT serum levels are observed. Although individuals with the Mmalton mutation usually have a heterogenous clinical presentation and very low levels of AAT, all the patients in this study were asymptomatic.

Keywords:

• Alpha 1 antitrypsin
• alpha 1 antitrypsin deficiency
• Mmalton
• asthma
• allergy

Additional information

Funding

This work was supported by grants from the Instituto de Salud Carlos III, Ministry of Health [FIS PI 12/01565 and FIS PI10/01718] with the funding of European Regional Development Fund-European Social Fund -FEDER-FSE]. E.H.B. was supported by a grant from Universidad de Las Palmas de Gran Canaria. The sponsors of the study had no role in designing the study, collecting, analyzing and interpreting the data, or writing the paper.