Characterization of the Mmalton carrier’s cohort within the EARCO (European Alpha- 1 Antitrypsin Research Collaboration) registry
(2025) In BMC Pulmonary Medicine 25(1).- 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... (More)
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.
(Less)
- author
- organization
- publishing date
- 2025-12
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Alpha-1 antitrypsin, Lung disease, PI*Mmalton, Registries
- in
- BMC Pulmonary Medicine
- volume
- 25
- issue
- 1
- article number
- 187
- publisher
- BioMed Central (BMC)
- external identifiers
-
- pmid:40269866
- scopus:105003175419
- ISSN
- 1471-2466
- DOI
- 10.1186/s12890-025-03651-8
- language
- English
- LU publication?
- yes
- id
- 348b5896-ab89-402e-8f50-30d802184722
- date added to LUP
- 2025-07-15 09:17:13
- date last changed
- 2025-07-15 09:17:33
@article{348b5896-ab89-402e-8f50-30d802184722,
abstract = {{<p>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.</p>}},
author = {{Ferraz, Beatriz D. and Sucena, Maria and Cardoso, Margarida Fonseca and Turner, Alice M. and Hernández-Pérez, José María and Torres-Duran, María and Tanash, Hanan and Rodríguez-García, Carlota and Jensen, Jens Ulrik and Corsico, Angelo and López-Campos, José Luis and Chapman, Kenneth and Clarenbach, Christian F. and Gomes, Joana and Miravitlles, Marc and Lara, Beatriz}},
issn = {{1471-2466}},
keywords = {{Alpha-1 antitrypsin; Lung disease; PI*Mmalton; Registries}},
language = {{eng}},
number = {{1}},
publisher = {{BioMed Central (BMC)}},
series = {{BMC Pulmonary Medicine}},
title = {{Characterization of the Mmalton carrier’s cohort within the EARCO (European Alpha- 1 Antitrypsin Research Collaboration) registry}},
url = {{http://dx.doi.org/10.1186/s12890-025-03651-8}},
doi = {{10.1186/s12890-025-03651-8}},
volume = {{25}},
year = {{2025}},
}