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Orphanet J Rare Dis. 2018 Jul 11;13(1):114. doi: 10.1186/s13023-018-0856-9.

Alpha-1 antitrypsin deficiency: outstanding questions and future directions.

Author information

1
Pulmonary Department, Hospital Álvaro Cunqueiro EOXI, Vigo, Spain.
2
NeumoVigo I+i Research Group, IIS Galicia Sur, Vigo, Spain.
3
Unidad Médico-Quirúrgica de Enfermedades Respiratorias, Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocio, Universidad de Sevilla, Sevilla, Spain.
4
CIBER de Enfermedades Respiratorias (CIBERES), Madrid, Spain.
5
Pneumology Department, Hospital Universitari Vall d'Hebron, Barcelona, Spain.
6
Molecular Genetics Unit, Instituto de Investigación de Enfermedades Raras (IIER), Instituto de Salud Carlos III (ISCIII), Madrid, Spain.
7
Fundación Investigación Hospital Clínico Valencia, Instituto de Investigación Sanitaria INCLIVA, c/Menéndez y Pelayo, 4, 46010, Valencia, Spain.
8
School of Medicine, Department of Physiology, Research group on Rare Respiratory Diseases (ERR), University of Valencia, Valencia, Spain.
9
School of Medicine, Department of Paediatrics, Obstetrics and Gynaecology, University of Valencia, Valencia, Spain.
10
Pneumology Department, Complejo Hospitalario Universitario de Pontevedra, Pontevedra, Spain.
11
Pneumology Department, Hospital Universitario San Cecilio, Granada, Spain.
12
Fundación Investigación Hospital Clínico Valencia, Instituto de Investigación Sanitaria INCLIVA, c/Menéndez y Pelayo, 4, 46010, Valencia, Spain. Francisco.Dasi@uv.es.
13
School of Medicine, Department of Physiology, Research group on Rare Respiratory Diseases (ERR), University of Valencia, Valencia, Spain. Francisco.Dasi@uv.es.

Abstract

BACKGROUND:

Alpha-1 antitrypsin deficiency (AATD) is a rare hereditary condition that leads to decreased circulating alpha-1 antitrypsin (AAT) levels, significantly increasing the risk of serious lung and/or liver disease in children and adults, in which some aspects remain unresolved.

METHODS:

In this review, we summarise and update current knowledge on alpha-1 antitrypsin deficiency in order to identify and discuss areas of controversy and formulate questions that need further research.

RESULTS:

1) AATD is a highly underdiagnosed condition. Over 120,000 European individuals are estimated to have severe AATD and more than 90% of them are underdiagnosed.

CONCLUSIONS:

2) Several clinical and etiological aspects of the disease are yet to be resolved. New strategies for early detection and biomarkers for patient outcome prediction are needed to reduce morbidity and mortality in these patients; 3) Augmentation therapy is the only specific approved therapy that has shown clinical efficacy in delaying the progression of emphysema. Regrettably, some countries reject registration and reimbursement for this treatment because of the lack of larger randomised, placebo-controlled trials. 4) Alternative strategies are currently being investigated, including the use of gene therapy or induced pluripotent stem cells, and non-augmentation strategies to prevent AAT polymerisation inside hepatocytes.

KEYWORDS:

Alpha-1 antitrypsin; Alpha-1 antitrypsin deficiency; Augmentation therapy; COPD; Cirrhosis; Panniculitis; Rare respiratory diseases; SERPINA1; Vasculitis

PMID:
29996870
PMCID:
PMC6042212
DOI:
10.1186/s13023-018-0856-9
[Indexed for MEDLINE]
Free PMC Article

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