Characteristics of diseases in children with inherited α1-antitrypsin deficiency




children, inherited α1-antitrypsin deficiency, diagnosis, therapy


The article presents the current views on genetics, features of metabolic disorders, course of various clinical manifestations, diagnostic criteria, and treatment principles for monogenic enzymopathy — an inherited α1;antitrypsin (AAT) deficiency.

Inherited AAT deficiency manifests itself as four clinical syndromes: respiratory disease (pulmonary emphysema, chronic obstructive pulmonary disease (COPD), bronchial asthma, spontaneous pneumothorax, bronchiectasis); liver disease and blood vessel damage. Respiratory disease manifests itself between the ages of 20–40 years. Chronic pulmonary emphysema is typical for homozygous PiZZ gene carriers. The most unfavorable clinical course variant including persistent cough, COPD development, bronchial asthma, pneumonia, co-existence of various respiratory diseases and severe disorders of external respiration is the PISZ phenotype. Bronchial asthma has severe clinical course with torpid purulent endobronchitis; is often uncontrolled despite background therapy. In COPD patients, exacerbations are frequent, severe, and prolonged. The reduction in the vessels of the pulmonary circulation results in pulmonary hypertension, right ventricular failure. In AAT deficiency, there is a high incidence of bronchiectasis, lung cancer. Liver diseases manifest themselves as neonatal hepatitis, biliary atresia, liver cirrhosis, infectious complications. Chronic form is characterized by subclinical changes in the biochemical parameters of liver function most of which (up to 70%) normalize before the age of 18 years. In patients until the age of 20 years, disease slowly progresses and leads to the development of liver cirrhosis in 30% of cases, while older patients develop liver cirrhosis in 30–50% of cases. Some patients have a benign course of liver disease and present with hepatomegaly.

Hemorrhagic syndrome occurs when protease inhibitor gene product acquires the properties of antithrombin. Vascular disease manifests itself as necrotizing panniculitis, severe hemorrhagic vasculitis with serum antineutrophil cytoplasmic antibodies to proteinase (С-АNСА). AAT deficiency may coexist with systemic vasculitis, vascular aneurysm, many other diseases, as well as with the development of aplastic processes of various localization.

In addition to clinical manifestations, diagnosis of inherited AAT deficiency includes screening programs, instrumental (X-ray, spirometry, ECG, ultrasound), laboratory (liver function, coagulation profile, immunogram, serum AAT concentration), genetic investigations, exclusion testing for cystic fibrosis, viral hepatitis, and other diseases.

Treatment of patients with inherited AAT deficiency consists in adequate nutrition and physical activity; treatment of pre-existing conditions; prevention and timely therapy for respiratory infections; pathogenetic therapy. Pathogenetic therapy for AAT deficiency is a replacement (augmentation) therapy with exogenous α1-antitrypsin concentrate. Replacement therapy is indicated only in patients >18 years of age with the PiZZ phenotype or other rare AAT phenotypes.

No conflict of interest was declared by the author.


Abaturov AE. (2011). Rol mestnykh ingibitorov proteaz v nespetsificheskoy zashchite respiratornogo trakta. Child's Health. 4: 117-124.

Alam S. Li Z, Atkinson C et al. (2014). Alpha 1-antitrypsin confers a proinflammatory phenotype that contributes to chronic obstructive pulmonary disease. Am.J.Respir.Crit.Care Med. 189, 8: 909-931.; PMid:24592811 PMCid:PMC4098095

Atkinson JJ, Lutey BA, Suzuki Y et al. (2011). The role of matrix metalloproteinase-9 in cigarette smoke - induced emphysema. Am.J.Respir.Crit.Care.Med. 83: 876-884.; PMid:21057003 PMCid:PMC3086754

Averyanov AV, Polivanova AE. (2006). Neytrofilnaya elastaza i bolezni organov dykhaniya. Pulmonologiya. 5: 74-77.

Balbi B, Ferraroti I, Miravitlles M. (2015). Efficacy of augmentation therapy for emphysema associated with α1-antitrypsin deficiency: enough is enough. Europen Respiratory Journal. 47 (1): 35-38.; PMid:26721962

Barrecheguren M, Miravitlles M. (2019). Treatment with inhaled a1-antitrypsin: a sguare peg in a round wole? European Respiratory Journal. 54 (5): 180-1894.; PMid:31754075

Blanko J. (2018). A well-designed/conducted study on alpha-1 antitrypsin epidemiology not quoted. Europen Respiratory Journal. 51; 3.; PMid:29519904

Bowick S, Bowick M. (2019). Living with Alpha-1-antitrypsin Deficiency. Columbia Southern University. 96p.; PMid:31754075

Campos MA, Kuppers F, Stocks JM et al. (2013). Safety and pharmacokinetics of 120 mg/kg versus 60 mg/kg weekly intravenosus infusions of alpha-1 proteinase inhibitor in alpha-1-antitrypsin deficiency: a multie center, randomized, double-blind, crossover study SPARK. COPD. 10 (6): 687-695.; PMid:23862647

Chuchalin AG. (2014). Sindrom defitsita alfa-1-antitripsina. Entsiklopediya redkikh zabolevaniy. Moscow: Littera: 672.

Cuvelier A, Muir JF, Hellot MF et al. (2000). Distribution of alpha-1-antitrypsin alleles in patients with bronchiectasis. Chest. 117: 415-419.; PMid:10669684

Dawwas MF, Davies SE, Griffirhs WJ et al. (2013). Prevalence and risk factors for liver involvement in individuals with PiZZ-related lung disease. Am.J.Respir.Crit.Care. Med. 187 (5): 502-508.; PMid:23262512

Didkovsky NA, Zharova MS, Kablashova NA, Malashenkova IK. (2011). A case of multiple genetic lesions in different systems of the lung defense. Pulmonologiya. 1: 111-114. URL:

Ferrarotti J, Ghun GA, Zorzetto M et al. (2012). Serum levers and genotype distribution of alpha-1-antitrypsin in the general population. Thorax. 67 (8): 669-674.; PMid:22426792

Greene CM, Hassan, Molloy TK et al. (2011). The role of proteases, endoplasmic reticulum stress and SERPI NA1 heterozygosity in lung disease and α1-antitrypsin deficiency. Exp.Rev.Respir.Med. 5 (3): 395-411.; PMid:21702661

Ivchik TV. (2011). About the genetics of pulmonary emphysema. Pulmonologiya. 4: 97-108.

Korytina GF, Akhmadishina LZ, Yanbaeva DG et al. (2008). Association of polymorphic variants of matrix metalloproteinase and antiprotease genes with development and severity of chronic obstructive pulmonary disease. Pulmonologiya. 1: 33-38.

Lin YC, Chiu WK, ChangH et al. (2008). Spontaneous pneumothorax in flight as first manifestation of alpha-1-antitrypsin deficiency. Aviat.Space.Environ.Med. 79: 704-706.; PMid:18619132

Migliazza L, Lopez SM, Murcia J et al. (2000). Long-term survival expectancy after liver transplantation in children. J Redial Surg. 35: 7-8.

Miraviteles M, Dirksen A, Ferrarotti I et al. (2017). European Respiratory Society statement: diagnosis and treatment of pulmonary disease in α1-antitrypsin deficiency. European Respiratory Journal. 50 (5): 1700610.; PMid:29191952

Nechayev VI. (2001). Emfizema legkikh: sistemnyye proyavleniya bolezni.Pulmonologiya. 9: 54-58.

Omesova OYu, Grabovskaya OV, Teplyuk NP et al. (2014). Pannikulit, obuslovlennyy defitsitom a1-antitripsina. Russian Journal of Skin and Venereal Diseases. 3: 32-35.

Ortega V, Pecchiari M. (2017). Understanding at-risk subgrourps for lung function impairment in life-long nonsmokers with α1-fntitrypsin deficiency. European Respiratory Journal. 49 (3): 17-114.; PMid:30573693

Ovcharenko SI, Son EA. (2011). Effects of alfa-1-antitripsin deficiency on lung disease. Pulmonologiya. 5: 79-86.

Palamarchuk GF, Akopov AP, Arsenyev AM et al. (2019). Bronkhoskopiya v diagnostike i lecheniyi zabolevaniy organov dykhaniya. SPb: Foliant: 328.

Pini L, Tiberio L, Venkatestan N et al. (2014). The role of bronchial epithelial cells in the pathogenesis of COPD in Z-alpha-1 antitrypsin deficiency. Respir.Res. 15 (1): 112.; PMid:25218041 PMCid:PMC4177581

Puzyrev VP, Savyuk VYa. (2003). Molekulyarnyye osnovy i klinicheskiye aspekty nedostatochnosti a1-antitripsina. Pulmonologiya. 1: 105-114.

Rozinova NN, Mizernitskiy YuL. (2015). Orfannyye zabolevaniya legkikh u detey. Moscow: ID MEDPRAKTIKA-M: 240.

Solov'eva OG. (2015). α1-Antitripsin deficiency in a pulmonologist' practice. Pulmonologiya. 25 (4): 505-508.

Spichak TV. (2005). Defitsit a1-AT pri boleznyakh legkikh u detey. Russian Pediatric Journal. 4: 30-33.

Struchkov PV, Drozdov DV, Lukina OF. (2019). Spirografiya: rukovodstvo. Moscow: GEOTAR-Media: 112.

Troyan VN. (2018). Klinicheskaya interpritatsiya rentgenografiyi: Spravochnik. Darbi M, ed. Moscow: GEOTAR-Media: 216.

Tymchenko AS. (2009). Perspektyvnist vykorystannia natyvnykh inhibitoriv proteiinaz z plazmy krovi, yak protyzapalnykh ta antyfermentnykh preparativ. Journal of the National Academy of Medical Sciences of Ukraine. 15 (3): 604-608.

Vershinina MV, Nechaeva GI, Grinberg LM, Govorova SE. (2012). Spontaneous pheumothorax and connective tissue dysplasia: molecular and genetic analysis. Pulmonologiya. 2: 34-39.

Vidal R, Blanco I, Casas F et al. (2008). Guidelines for the diagnosis and management of α1-antitrypsin deficiency. Pulmonologiya. 1: 14-28.

Zaynudinov ZM, Zhurkova NV, Kaganov BS. (2009). Nedostatochnost alfa-1-antitripsina u detey. Voprosy prakticheskoy pediatriyi. 4 (4): 67-70.

Zhigaltsova-Kuchinskaya OA, Sivitskaya LN, Danilenko NG et al. (2015). Alpha-1-antitrypsin deficiency: genetic fundamentals, epidemiology, role in the development of bronchopulmonary pathology. Vestnik VGMU. 14: 39-52.

Zhurkova NV, Kondakova OB, Strokova TV et al. (2008). Nedostatochnost a1-antitripsina u detey s patologiyey pecheni. Pediatria Journal Named after G.N. Speransky. 87 (3): 138-141.