[MIM 613 490]

Estimated prevalence of 1/5,000 in Europe.  Autosomal dominant transmission of a mutation of the SERPINA1 gene (14q32.13) resulting in plasma deficiency of α1-antitrypsin, a glycoprotein of the serpine group that inhibits proteases, particularly elastase. More than 100 variants of the SERPINA1 gene can cause the absence of circulating α1-antitrypsin (null alleles), low AAT secretion by the hepatocytes (deficient alleles) or even altered inhibitory activity of the enzyme (dysfunctional alleles). Low levels of alpha-1-antitrypsin, involved in the regulation of elastase and proteinase 3 inside the neutrophils, lead to alveolar damage.

The severe form, called Z-AATD, is caused by the homozygous Z variant of the gene and  has a very heterogeneous evolution. Some individuals remain healthy, while others develop lung or liver disease, rarely both.

• liver disease: typically occurs in newborns or during infancy (cholestasis) or later in adult life (typically at ≥ 40 years of age). Z-AATD can cause neonatal cholestasis in about 10 % of the affected infants and about 30-50 % of them will develop progressive chronic liver disease. About 10 % of the adults develop cirrhosis or hepatocellular carcinoma. 

• lung disease usually manifests itself between 20 and 50 years of age. The main manifestations are early panacinar emphysema, bronchiectasis, bronchial asthma or vasculitis, which are manifested by dyspnea, cough, wheezing and persistent sputum. Smoking, associated with an earlier onset, is a major factor affecting the course of the pulmonary manifestations. Other features are weight loss, recurrent respiratory infections and fatigue.
• panniculitis of varying severity can occur at any age
• more rarely: vascular involvement related to the degradation of the media of the vessel walls, and glomerular renal lesions with nephrotic syndrome

Treatments:

• healthy lifestyle, bronchodilators in case of pulmonary involvement
• severe cases: weekly IV injection of α1-antitrypsin (Alfalastin, Respreeza® or Prolastin-C®)
• hepatic injury: subcutaneous administration of fazirsiran decreases intrahepatic accumulation of mutant protein and liver fibrosis
• liver or lung transplantation

Anesthetic implications: 

according to the severity of the involvement

-        pulmonary: SpO2 at room air, bronchodilators, chest physiotherapy

-        hepatic: check liver enzymes, bilirubin, proteins, portal hypertension ?

References : 

-        Myles PS, Weeks AM. 
Alpha 1-antitrypsin deficiency: circulatory arrest following induction of anaesthesia. 
Anaesth Intensive Care 1992; 20:358-62. 

-        Strnad P, McElvaney NG, Lomas DA.
Alpha1-Antitrypsin deficiency.
N Engl J Med 2020; 382:1443-55 

-        Strnad P, Mandorfer M, Choudhury G, Griffiths  W, Trautwein C, Loomba R et al. 
Fazirsiran for liver disease associated with alpha1-antitrypsin deficiency.
N Engl J Med 2022 ;387 :514-24.

Updated: February 2023