Researchers recently discovered a Q0parma mutation in 3 patients with alpha-1 antitrypsin deficiency (AATD) presenting with pulmonary manifestations and published their results in Respirology Case Reports.

This finding helps expand the list of null alleles known to occur within the serpin family A member 1 (SERPINA1) gene, underlining the importance of genetic screening and implementation of target detection studies to better understand the rare mutations of alpha-1 antitrypsin (AAT) to identify and treat individuals at the earliest possible stage. A Q0parma allele consists of the deletion of codon valine 413.

Aiello et al studied 3 subjects: a 62-year-old male referred to the University Hospital Parma Medical Center in Ohio for severe emphysema with respiratory failure; and his offspring, a 32-year-old female and a 28-year-old male having both been diagnosed with AATD following the genotype analysis performed on the father of the subjects. 


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Read more about AATD etiology

The authors performed biochemical and genetic tests to confirm the presence of AATD, and the samples submitted underwent a diagnostic algorithm that comprises the determination of AAT and C-reactive protein serum levels, the phenotyping by isoelectric focusing analysis, the genotyping for the detection of S and Z variants or AAT genotyping test and, when needed, SERPINA1 gene sequencing.

“This study points out the importance of genotyping by whole SERPINA1 gene sequencing, in addition to serum AAT determination, in order to enable detection of AATD in populations and to recommend additional AAT replacement therapy,” the authors said.

“Augmentation therapy is proved to be effective in improving the quality of life and in slowing down the disease progression, as seen in case 1 chest high resolution computed tomography scan at diagnosis and after 5 years of augmentation therapy.”

The main function of AAT is to protect the lung parenchyma from proteolytic degradation. The gene encoding AAT is the highly polymorphic SERPINA1 gene. Mutations in the SERPINA1 gene can lead to AATD, a common hereditary disorder but largely under-recognized despite the recommendations of both the World Health Organization and the medical societies of the United States and Europe. This deficiency is an autosomal, codominant disorder that has several mutations of the SERPINA1 gene associated with the development of pulmonary emphysema, chronic liver disease, and/or cirrhosis.

Reference

Aiello M, Frizzelli A, Marchi L, et al. Clinical manifestations of a new alpha‐1 antitrypsin genetic variant: Q0parma. Respirol Case Rep. Published online April 14, 2022. doi:10.1002/rcr2.936