Skip to
  1. Homepage
  2. Rare diseases
  3. Search
Simple search

Simple search

*
(*) mandatory field





 

Other search option(s)

Alpha-1-antitrypsin deficiency

Orpha number ORPHA60
Synonym(s) -
Prevalence 1-5 / 10 000
Inheritance
  • Autosomal recessive
Age of onset Variable
ICD-10
  • E88.0
OMIM
UMLS
  • C0221757
MeSH
  • C531610
  • D019896
MedDRA
  • 10001806
SNOMED CT
  • 30188007

Summary

Alpha-1-antitrypsin deficiency (AATD) is a genetic disorder that manifests as pulmonary emphysema, liver cirrhosis and, rarely, as the skin disease panniculitis, and is characterized by low serum levels of AAT, the main protease inhibitor (PI) in human serum. The prevalence in the general population in Western Europe is approximately 1 in 2,500, and is highly dependent on the Scandinavian descent within the population. The most common deficiency alleles in North Europe are PI Z and PI S, and the majority of individuals with severe AATD are PI type ZZ. The clinical manifestations may vary widely between patients, ranging from asymptomatic in some to fatal liver or lung disease in others. Type ZZ and SZ AATD are risk factors for the development of respiratory symptoms (dyspnoea, coughing), early onset emphysema, and airflow obstruction early in adult life. Environmental factors such as cigarette smoking, and dust exposure are additional risk factors and have been linked to an accelerated progression of this condition. Type ZZ AATD may also lead to the development of acute or chronic liver disease in childhood or adulthood: prolonged jaundice after birth with conjugated hyperbilirubinemia and abnormal liver enzymes are characteristic clinical signs. Cirrhotic liver failure may occur around age 50. In very rare cases, necrotizing panniculitis and secondary vasculitis may occur. AATD is caused by mutations in the SERPINA1 gene (14q32.1) encoding AAT, and is inherited as an autosomal recessive trait. The diagnosis can be established by detection of low serum levels of AAT and isoelectric focusing. Differential diagnoses should exclude bleeding disorders or jaundice, viral infection, hemochromatosis, Wilson's disease and autoimmune hepatitis (see these terms). For treatment of lung disease, intravenous alpha-1-antitrypsin augmentation therapy, annual flu vaccination and a pneumococcal vaccine every 5 years are recommended. Relief of breathlessness may be obtained with long-acting bronchodilators and inhaled corticosteroids. The end-stage liver and lung disease can be treated by organ transplantation. In AATD patients with cirrhosis, prognosis is generally severe.

Expert reviewer(s)

  • Dr Laura FREGONESE
  • Dr Jan STOLK

(*) Required fields.

Attention: Only comments seeking to improve the quality and accuracy of information on the Orphanet website are accepted. For all other comments, please send your remarks via contact us. Only comments written in English can be processed.


Captcha image

Detailed information

Summary information
Emergency guidelines
  • ES (2010,pdf)
  • FR (2010,pdf)
  • EN (2010,pdf)
  • DE (2014,pdf)
  • IT (2012,pdf)
Review article
  • EN (2008)
Guidance for genetic testing
  • EN (2011,pdf)
Clinical genetics review
  • EN (2014)
Get Acrobat Reader
The documents contained in this web site are presented for information purposes only. The material is in no way intended to replace professional medical care by a qualified specialist and should not be used as a basis for diagnosis or treatment.