[Alpha-1 antitrypsin deficiency caused by Null mutation]

Abstract

Introduction: Alpha-1 antitrypsin deficiency is a hereditary disease defined at the biological level by a serum alpha-1 antitrypsin level below 11μM/L. The null variants are characterized by undetectable circulating alpha-1 antitrypsin levels. Suspicion of a null variant requires the use of appropriate diagnostic techniques.

Case report: We report the case of a 33-year old patient presenting with dyspnea on exertion, associated with a moderate airflow obstruction, incompletely reversible. His tobacco use was less than 3pack-years. The thoracic CT-scan showed emphysema. The serum alpha-1 antitrypsin level was collapsed. Phenotyping by isoelectrofocusing on agarose gels did not show any band. The study of the SERPINA1 gene, by PCR-sequence of the II, III, IV and V exons and the flanking intronic sequences, allowed identification of the NullQ0ourém allele in homozygous state. This mutation was found in heterozygous state in both parents of the index case and in one of his brothers. The index case showed a rapid aggravation of the airflow obstruction.

Conclusion: In the case of a serum alpha-1 antitrypsin deficiency, the analysis of the phenotype of the protein by isoelectrofocusing must be performed as a first-line investigation. The detection of an atypical profile may suggest the presence of deficient alleles other than the PI S and PI Z alleles that can only be characterized by sequencing of the whole SERPINA1 gene. The patients carrying a null mutation have a high risk of severe chronic obstructive pulmonary disease.

Keywords: Alpha-1 antitrypsin deficiency; Déficit en alpha-1 antitrypsine; Genotyping; Génotypage; Mutation Null; Null mutation; PI phenotype; Phénotype PI; SERPINA1.