Characterization of the Mmalton carrier's cohort within the EARCO (European Alpha- 1 Antitrypsin Research Collaboration) registry
Ferraz, Beatriz D Sucena, Maria Cardoso, Margarida Fonseca Turner, Alice M Hernández-Pérez, José María Torres-Duran, María Tanash, Hanan Rodríguez-García, Carlota Jensen, Jens-Ulrik Corsico, Angelo
Ferraz, Beatriz D
Sucena, Maria
Cardoso, Margarida Fonseca
Turner, Alice M
Hernández-Pérez, José María
Torres-Duran, María
Tanash, Hanan
Rodríguez-García, Carlota
Jensen, Jens-Ulrik
Corsico, Angelo
Affiliation
Unidade Local de Saúde de Santo António; Universidade Do Porto; University Hospitals Birmingham NHS Foundation Trust; University of Birmingham; Hospital Universitario Nuestra Señora de La Candelaria; Hospital Álvaro Cunqueiro; Instituto de Salud Carlos III; Lund University; Skåne University Hospital; Complejo Hospitalario Clínico-Universitario de Santiago; Instituto de Investigación Sanitaria de Santiago de Compostela; University of Copenhagen; Herlev and Gentofte Hospital; San Matteo Hospital Foundation; University of Pavia; Hospital Universitario Virgen del Rocío; Universidad de Sevilla; University of Toronto; University Health Network; University Hospital Zurich; Hospital Universitari Vall d'Hebron; University Hospitals of Coventry and Warwickshire
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Publication date
2025-04-23
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Abstract
Introduction: The PI*Mmalton variant is a rare form of alpha-1-antitrypsin (AAT) deficiency, caused by a mutation in the SERPINA1 gene and associated with reduced AAT levels. Its clinical significance remains uncertain due to the limited number of reported cases.
Methods: This study characterizes PI*Mmalton carriers within the EARCO (European Alpha-1 Antitrypsin Research Collaboration) registry and compares them with PI*ZZ individuals. Patients were categorized into moderate PI*Mmalton (combined with PI*S or PI*I) and severe PI*Mmalton (combined with PI*Z, PI*Mmalton, PI*MProcida, or PI*MHerleen). Demographic data, lung function, respiratory symptoms, disease prevalence, and augmentation therapy use were analyzed.
Results: Among 2074 individuals, 59 (2.8%) carried a PI*Mmalton allele. Severe PI*Mmalton patients exhibited lung function impairment comparable to PI*ZZ individuals, with a significantly lower FEV₁/FVC ratio (55.9% vs. 57.6%) and similar AAT levels (~ 25 mg/dL). Moderate PI*Mmalton patients had better lung function and higher AAT levels (median 54 mg/dL). Emphysema was more prevalent in severe PI*Mmalton (54.5%) and PI*ZZ (61.2%) than in moderate PI*Mmalton (34.6%). Augmentation therapy use was highest in severe PI*Mmalton (45.2%). Liver disease prevalence was comparable across groups.
Conclusion: Severe PI*Mmalton patients exhibit clinical and functional similarities to PI*ZZ individuals, suggesting a comparable disease burden. Moderate PI*Mmalton patients, however, show milder impairment. These findings reinforce the need for genotype-specific management strategies and suggest that PI*Mmalton carriers, particularly those with severe variants, should be considered in future clinical trials.
Citation
Ferraz BD, Sucena M, Cardoso MF, Turner AM, Hernández-Pérez JM, Torres-Duran M, Tanash H, Rodríguez-García C, Jensen JU, Corsico A, López-Campos JL, Chapman K, Clarenbach CF, Gomes J, Miravitlles M, Lara B. Characterization of the Mmalton carrier's cohort within the EARCO (European Alpha- 1 Antitrypsin Research Collaboration) registry. BMC Pulm Med. 2025 Apr 23;25(1):187. doi: 10.1186/s12890-025-03651-8.
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Article