SERPINA1 Q0Q0 clinical presentation of a very rare alpha-1 antitrypsin deficiency

<bold>Background:</bold> The Q0Q0 AATD genotype relates to undetectable protein level. Although genetically characterized, its clinical expression is unreported. Since strategies directed at the liver in ZZ will shut-off SERPINA1 transcription it is of outmost importance to describe it Methods: Collaborative study involving 4 laboratories: Marburg, Pavia, Lille, Lyon. <bold>Results:</bold> 33 patients, 52% female, 48% smokers. Countries of origin: Greece 10 patients, Italy 9, Morocco 4, Austria 2, Portugal 2, Egypt, Romania, Belgium, North Africa, France and Germany 1 (Mediterranean ascend 79%). Emphysema alone was reported in 24, with bronchiectasis 13, with bronchial asthma 5, panniculitis 1. Environmental-professional exposure identified in 46%. Median age at diagnosis (IQR 25-75) 37 years, median %-predicted FEV1 and DLCO, 42 (IQR 29-63) and 46 (IQR 33-56) respectively. Augmentation therapy in 55%, 78% once a week. Median survival (months) was 63 (31.5-180), median treatment duration 91 (30.5-276) months. Alive were 22 patients. Survival related to FEV1 at diagnosis (p=0.028). Genotyping disclosed:9 Q0Amersfoort/Q0Amersfoort, 7 Q0Cairo/Q0Cairo, 6 Q0ourem/Q0ourem, 2 Q0Granitefalls/Q0Granitefalls, 2 Q0Brescia/Q0Brescia, 2 Q0Bellingham/Q0Belingham and a single patient with: Q0Lampedusa/Q0Lampedusa, Q0Clayton/Q0Clayton, Q0Casablanca/Q0Casablanca, Q0Clayton/Q0Achicourt, Q0Mattawa/Q0Amersfoort. <bold>Conclusion:</bold> Q0/Q0 genotype relates to severe emphysema even in non-smokers. FEV1 predicts prognosis. Epidemiologically is distributed in the Mediterranean "lakeline" and prevails in Greece and Italy likely to be related to ancient Greeks’ migrations. ZZ patient lungs treated with shut-off transcription strategies should be protected