Researchers in Germany described a new genetic variant causing alpha-1 antitrypsin deficiency (AATD) called PiQ0Heidelberg, as published in Respiratory Medicine Case Reports. This variant was previously identified but not clinically described.

The patient was a 77-year-old woman who was classified with Global Initiative for Chronic Obstructive Lung Disease grade 3. She also had group B chronic obstructive pulmonary disease, severe destructive panlobular emphysema, and respiratory failure on exertion. She had no history of heavy smoking.

Genetic analysis revealed that she had a rare mutation (c.-5+5 G > A) in the SERPINA1 gene. Her serum alpha-1 antitrypsin (AAT) level was 0.1 g per L, well below the reference values of 0.9 g per L to 2.0 g per L. Isoelectric focusing showed that she only had the Z-protein, which indicated that she had a null mutation.


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“AATD is underdiagnosed,” the researchers wrote. “Wider testing could help delay some clinical sequelae by allowing earlier therapeutic and lifestyle interventions.” The woman was treated with AAT replacement therapy following diagnosis.

Read more about the AATD etiology

AATD is a rare genetic disease caused by a mutation in the SERPINA1 gene, which normally produces the AAT enzyme. This enzyme is responsible for protecting the lungs from the activity of elastase.

When the body cannot produce enough AAT because of the SERPINA1 mutations, the lung parenchyma becomes damaged due to the activity of elastase, and gas exchange can deteriorate over time. The majority of the population have the M-allele of the SERPINA1 gene, which is associated with normal levels of AAT in the serum.

The most common pathogenic alleles are the S and Z alleles. The S allele causes a 40% reduction in serum AAT levels, while the Z allele causes a 90% reduction. To date, more than 120 mutations have been identified that can cause AATD.

Reference

Presotto MA, Veith M, Trinkmann F, et al. Clinical characterization of a novel alpha1-antitrypsin null variant: PiQ0Heidelberg. Respir Med Case Rep. 2022;3(35):101570. doi:10.1016/j.rmcr.2021.101570