Alpha 1 Antitrypsin deficiency associated with the Mmalton variant: an EARCO Research project.

<bold>Introduction:</bold> Pi*Mmalton is a rare variant of alpha-1-antitrypsin (AAT) deficiency, associated with low AAT levels. However, little is known about this variant. Our study aims to analyze all the patients with at least one Pi*Mmalton allele registered in EARCO and compare them with Pi*ZZ regarding demographic, clinical, and lung function parameters. <bold>Methods:</bold> We analyzed data from the EARCO registry until September 2023. <bold>Results:</bold> We identified 59 (2.84%) Pi*Mmalton patients (64.4% men;mean age 52±17.1 yo), predominantly ex-smokers (63.8%), mean pack year of 20. Mmalton/M patients were excluded, and the majority were Mmalton/S(42%) and Mmalton/Z(41%). Median AAT level of 25 (22-54) mg/dL. In 67.8%, there was lung disease, particularly physician-diagnosed COPD (47.5%), emphysema (45.8%) and bronchiectasis (13.6%). They exhibited a mild obstructive pattern (mean FEV1 73.4%; FEV1/FVC 0.62), with mild DLCO impairment (mean DLCO 69.9%), and they were relatively asymptomatic (mean CAT 8.4 and mean BODEx 1.6). When compared with Pi*ZZ, Pi*Mmalton individuals had a similar smoking history and similar AAT levels (p>0.05) but higher pack-years (20 versus 15, p=0.010). Emphysema was less prevalent in Pi*Mmalton (45.8%)when compared to Pi*ZZ patients (61.2%, p=0.028), but similar rates of COPD, asthma, and bronchiectasis. Although they had similar rates of exacerbations and lung function they were less symptomatic than Pi*ZZ patients, with lower CAT (8.4±7.5 vs 13.5±9.6, p<0.001) and BODEx scores (1.6±1.5 vs 2.0±2.0, p=0.043). <bold>Conclusion:</bold> Pi*Mmalton patients, like Pi*ZZ, have a low level of AAT and a high risk of developing obstructive lung disease. However, they were less symptomatic than Pi*ZZ patients.