Novel mutation (M_angera-E288V) in alpha-1 antitrypsin deficiency

Alpha-1 antitrypsin deficiency is an autosomal, codominant disorder caused by mutations of the SERPINA1 gene. Several mutations have been described associated with the development of pulmonary and/or chronic liver diseases. We report a novel mutation Mangera, identified for the first time in an Italian patient originating from the city of Angera (Varese), Italy.

This case report describes a 64-year-old Italian male, a lifelong non-smoker, diagnosed with severe alpha-1 antitrypsin deficiency (AATD) as composed heterozygous with S allele and a novel mutation named Mangera. The patient presented with exertional dyspnea and had reduced serum AAT levels (0.54 g/L). Pulmonary function tests indicated mild airway obstruction with preserved diffusion capacity, and chest CT scans revealed early centrilobular emphysema and fibrotic changes. Genetic analysis was performed, finding a previously unreported mutation. Despite the severe AAT deficiency, the patient exhibited no significant clinical, radiological, or functional deterioration. Given the absence of disease progression, augmentation therapy was deferred in favor of ongoing annual monitoring.

This case report highlights the necessity of referring patients to specialized centers equipped with the expertise and tools required for precise diagnosis. Furthermore, the identification of the Mangera mutation expands the spectrum of known SERPINA1 variants associated with severe AATD, emphasizing the ongoing need for vigilance and thorough investigation in cases of suspected deficiency.