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Alpha-1-antitrypsin deficiency(A1ATD)

MedGen UID:
67461
Concept ID:
C0221757
Disease or Syndrome
Synonyms: A1AT deficiency; A1ATD; AAT deficiency; Alpha1-Antitrypsin Deficiency
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
Concept ID:
C0441748
Intellectual Product
Sources: HPO, OMIM, Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in homozygotes. In the context of medical genetics, autosomal recessive disorders manifest in homozygotes (with two copies of the mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele).
Autosomal recessive inheritance (HPO, OMIM, Orphanet)
SNOMED CT: Alpha-1-antitrypsin deficiency (30188007); alpha-1-Proteinase inhibitor deficiency (30188007)
 
Gene (location): SERPINA1 (14q32.13)
OMIM®: 613490
Orphanet: ORPHA60

Disease characteristics

Excerpted from the GeneReview: Alpha-1 Antitrypsin Deficiency
Alpha-1 antitrypsin deficiency (AATD) is characterized by an increased risk for: chronic obstructive pulmonary disease (i.e., emphysema, persistent airflow obstruction, and/or chronic bronchitis) in adults; liver disease in children and adults; panniculitis; and c-ANCA positive vasculitis. Emphysema, sometimes with associated bronchiectasis, is the most common manifestation of AATD. Smoking is the major factor influencing the course of chronic obstructive pulmonary disease (COPD). The onset of respiratory disease in smokers with AATD is characteristically between ages 40 and 50 years; in non-smokers, the onset can be delayed to the sixth decade, and some non-smokers never develop COPD. Non-smokers may have a normal life span. Although reported, emphysema in children with AATD is extremely rare. AATD-associated liver disease, which is present in only a small portion of affected children, manifests as obstructive jaundice and increased serum aminotransferase levels in the early days and months of life. The incidence of liver disease increases with age. Liver disease in adults (manifesting as cirrhosis and fibrosis) may occur in the absence of a history of neonatal or childhood liver disease. The risk for hepatocellular carcinoma (HCC) is increased in individuals with AATD. [from GeneReviews]
Authors:
James K Stoller  |  Felicitas L Lacbawan  |  Loutfi S Aboussouan   view full author information

Additional descriptions

From OMIM
Alpha-1-antitrypsin deficiency is an autosomal recessive disorder. The most common manifestation is emphysema, which becomes evident by the third to fourth decade. A less common manifestation of the deficiency is liver disease, which occurs in children and adults, and may result in cirrhosis and liver failure. Environmental factors, particularly cigarette smoking, greatly increase the risk of emphysema at an earlier age (Crystal, 1990).  http://www.omim.org/entry/613490
From GHR
Alpha-1 antitrypsin deficiency is an inherited disorder that may cause lung disease and liver disease. The signs and symptoms of the condition and the age at which they appear vary among individuals.People with alpha-1 antitrypsin deficiency usually develop the first signs and symptoms of lung disease between ages 20 and 50. The earliest symptoms are shortness of breath following mild activity, reduced ability to exercise, and wheezing. Other signs and symptoms can include unintentional weight loss, recurring respiratory infections, fatigue, and rapid heartbeat upon standing. Affected individuals often develop emphysema, which is a lung disease caused by damage to the small air sacs in the lungs (alveoli). Characteristic features of emphysema include difficulty breathing, a hacking cough, and a barrel-shaped chest. Smoking or exposure to tobacco smoke accelerates the appearance of emphysema symptoms and damage to the lungs.About 10 percent of infants with alpha-1 antitrypsin deficiency develop liver disease, which often causes yellowing of the skin and whites of the eyes (jaundice). Approximately 15 percent of adults with alpha-1 antitrypsin deficiency develop liver damage (cirrhosis) due to the formation of scar tissue in the liver. Signs of cirrhosis include a swollen abdomen, swollen feet or legs, and jaundice. Individuals with alpha-1 antitrypsin deficiency are also at risk of developing a type of liver cancer called hepatocellular carcinoma.In rare cases, people with alpha-1 antitrypsin deficiency develop a skin condition called panniculitis, which is characterized by hardened skin with painful lumps or patches. Panniculitis varies in severity and can occur at any age.  https://ghr.nlm.nih.gov/condition/alpha-1-antitrypsin-deficiency

Clinical features

Liver Cirrhosis
MedGen UID:
7368
Concept ID:
C0023890
Disease or Syndrome
Cirrhosis is scarring of the liver. Scar tissue forms because of injury or long-term disease. Scar tissue cannot do what healthy liver tissue does - make protein, help fight infections, clean the blood, help digest food and store energy. Cirrhosis can lead to . -Easy bruising or bleeding, or nosebleeds. -Swelling of the abdomen or legs . -Extra sensitivity to medicines. -High blood pressure in the vein entering the liver. -Enlarged veins called varices in the esophagus and stomach. Varices can bleed suddenly. - Kidney failure. -Jaundice. -Severe itching. -Gallstones. A small number of people with cirrhosis get liver cancer. Your doctor will diagnose cirrhosis with blood tests, imaging tests, or a biopsy. Cirrhosis has many causes. In the United States, the most common causes are chronic alcoholism and hepatitis. Nothing will make the scar tissue disappear, but treating the cause can keep it from getting worse. If too much scar tissue forms, you may need to consider a liver transplant. . NIH: National Institute of Diabetes and Digestive and Kidney Diseases.
Elevated hepatic transaminases
MedGen UID:
338525
Concept ID:
C1848701
Finding
Elevations of the levels of SGOT and SGPT in the serum. SGOT (serum glutamic oxaloacetic transaminase) and SGPT (serum glutamic pyruvic transaminase) are transaminases primarily found in the liver and heart and are released into the bloodstream as the result of liver or heart damage. SGOT and SGPT are used clinically mainly as markers of liver damage.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVAlpha-1-antitrypsin deficiency
Follow this link to review classifications for Alpha-1-antitrypsin deficiency in Orphanet.

Professional guidelines

PubMed

Janciauskiene S, Ferrarotti I, Laenger F, Jonigk D, Luisetti M
Eur J Hum Genet 2011 May;19(5) Epub 2011 Jan 19 doi: 10.1038/ejhg.2010.246. PMID: 21248733Free PMC Article
Stoller JK, Snider GL, Brantly ML, Fallat RJ, Stockley RA, Turino GM, Konietzko N, Dirksen A, Eden E, Fallat RJ, Luisetti M, Stolk J, Strange C; American Thoracic Society.; European Respiratory Society.
Pneumologie 2005 Jan;59(1):36-68. doi: 10.1055/s-2004-830176. PMID: 15685488

External

Orphanet, Alpha-1 antitrypsin deficiency, 2010

Recent clinical studies

Etiology

Al-Jameil N, Hassan AA, Buhairan A, Hassanato R, Isac SR, Al-Otaiby M, Al-Maarik B, Al-Ajeyan I
Medicine (Baltimore) 2017 Feb;96(6):e6071. doi: 10.1097/MD.0000000000006071. PMID: 28178162Free PMC Article
Barrecheguren M, Monteagudo M, Simonet P, Llor C, Rodriguez E, Ferrer J, Esquinas C, Miravitlles M
Int J Chron Obstruct Pulmon Dis 2016 May 10;11:999-1004. doi: 10.2147/COPD.S108505. PMID: 27274221Free PMC Article
Topic A, Nagorni-Obradovic L, Francuski D, Ljujic M, Malic Z, Radojkovic D
Biochem Genet 2016 Oct;54(5):746-52. Epub 2016 Jun 6 doi: 10.1007/s10528-016-9748-7. PMID: 27271084
Hampson JA, Stockley RA, Turner AM
Respir Res 2016 Mar 31;17:34. doi: 10.1186/s12931-016-0348-1. PMID: 27036487Free PMC Article
Greulich T, Vogelmeier CF
Ther Adv Respir Dis 2016 Feb;10(1):72-84. Epub 2015 Sep 4 doi: 10.1177/1753465815602162. PMID: 26341117

Diagnosis

Al-Jameil N, Hassan AA, Buhairan A, Hassanato R, Isac SR, Al-Otaiby M, Al-Maarik B, Al-Ajeyan I
Medicine (Baltimore) 2017 Feb;96(6):e6071. doi: 10.1097/MD.0000000000006071. PMID: 28178162Free PMC Article
Kueppers F, Sanders C
Allergy Asthma Proc 2017 Mar 24;38(2):108-114. Epub 2017 Jan 24 doi: 10.2500/aap.2017.38.4031. PMID: 28120746
Barrecheguren M, Monteagudo M, Simonet P, Llor C, Rodriguez E, Ferrer J, Esquinas C, Miravitlles M
Int J Chron Obstruct Pulmon Dis 2016 May 10;11:999-1004. doi: 10.2147/COPD.S108505. PMID: 27274221Free PMC Article
Hampson JA, Stockley RA, Turner AM
Respir Res 2016 Mar 31;17:34. doi: 10.1186/s12931-016-0348-1. PMID: 27036487Free PMC Article
Greulich T, Vogelmeier CF
Ther Adv Respir Dis 2016 Feb;10(1):72-84. Epub 2015 Sep 4 doi: 10.1177/1753465815602162. PMID: 26341117

Therapy

Norton B, Denson J, Briggs C, Bowles M, Stell D, Aroori S
World J Gastroenterol 2016 Mar 21;22(11):3289-95. doi: 10.3748/wjg.v22.i11.3289. PMID: 27004008Free PMC Article
Zuo L, Pannell BK, Zhou T, Chuang CC
Gene 2016 Sep 10;589(2):118-22. Epub 2016 Jan 5 doi: 10.1016/j.gene.2016.01.004. PMID: 26768576
Greulich T, Vogelmeier CF
Ther Adv Respir Dis 2016 Feb;10(1):72-84. Epub 2015 Sep 4 doi: 10.1177/1753465815602162. PMID: 26341117
Craig TJ
J Allergy Clin Immunol Pract 2015 Jul-Aug;3(4):506-11. Epub 2015 May 29 doi: 10.1016/j.jaip.2015.04.005. PMID: 26032475
Cathomas M, Schüller A, Candinas D, Inglin R
Int Wound J 2015 Oct;12(5):601-4. Epub 2015 Mar 26 doi: 10.1111/iwj.12419. PMID: 25818083

Prognosis

Topic A, Nagorni-Obradovic L, Francuski D, Ljujic M, Malic Z, Radojkovic D
Biochem Genet 2016 Oct;54(5):746-52. Epub 2016 Jun 6 doi: 10.1007/s10528-016-9748-7. PMID: 27271084
Hampson JA, Stockley RA, Turner AM
Respir Res 2016 Mar 31;17:34. doi: 10.1186/s12931-016-0348-1. PMID: 27036487Free PMC Article
Norton B, Denson J, Briggs C, Bowles M, Stell D, Aroori S
World J Gastroenterol 2016 Mar 21;22(11):3289-95. doi: 10.3748/wjg.v22.i11.3289. PMID: 27004008Free PMC Article
Stone HM, Edgar RG, Thompson RD, Stockley RA
COPD 2016;13(2):146-52. Epub 2015 Oct 21 doi: 10.3109/15412555.2015.1048850. PMID: 26488418
Milger K, Holdt LM, Teupser D, Huber RM, Behr J, Kneidinger N
Int J Chron Obstruct Pulmon Dis 2015 May 7;10:891-7. doi: 10.2147/COPD.S80173. PMID: 26005342Free PMC Article

Clinical prediction guides

Al-Jameil N, Hassan AA, Buhairan A, Hassanato R, Isac SR, Al-Otaiby M, Al-Maarik B, Al-Ajeyan I
Medicine (Baltimore) 2017 Feb;96(6):e6071. doi: 10.1097/MD.0000000000006071. PMID: 28178162Free PMC Article
Topic A, Nagorni-Obradovic L, Francuski D, Ljujic M, Malic Z, Radojkovic D
Biochem Genet 2016 Oct;54(5):746-52. Epub 2016 Jun 6 doi: 10.1007/s10528-016-9748-7. PMID: 27271084
Hampson JA, Stockley RA, Turner AM
Respir Res 2016 Mar 31;17:34. doi: 10.1186/s12931-016-0348-1. PMID: 27036487Free PMC Article
Stone HM, Edgar RG, Thompson RD, Stockley RA
COPD 2016;13(2):146-52. Epub 2015 Oct 21 doi: 10.3109/15412555.2015.1048850. PMID: 26488418
Cathomas M, Schüller A, Candinas D, Inglin R
Int Wound J 2015 Oct;12(5):601-4. Epub 2015 Mar 26 doi: 10.1111/iwj.12419. PMID: 25818083

Recent systematic reviews

North TL, Ben-Shlomo Y, Cooper C, Deary IJ, Gallacher J, Kivimaki M, Kumari M, Martin RM, Pattie A, Sayer AA, Starr JM, Wong A, Kuh D, Rodriguez S, Day IN
J Med Genet 2016 Apr;53(4):280-8. Epub 2016 Feb 1 doi: 10.1136/jmedgenet-2015-103342. PMID: 26831755Free PMC Article
Wozniak J, Wandtke T, Kopinski P, Chorostowska-Wynimko J
Hum Gene Ther 2015 Nov;26(11):709-18. Epub 2015 Sep 29 doi: 10.1089/hum.2015.044. PMID: 26413996Free PMC Article
Bradi AC, Audisho N, Casey DK, Chapman KR
COPD 2015 May;12 Suppl 1:15-21. doi: 10.3109/15412555.2015.1021908. PMID: 25938286
Casas F, Blanco I, Martínez MT, Bustamante A, Miravitlles M, Cadenas S, Hernández JM, Lázaro L, Rodríguez E, Rodríguez-Frías F, Torres M, Lara B
Arch Bronconeumol 2015 Apr;51(4):185-92. Epub 2014 Jul 12 doi: 10.1016/j.arbres.2014.05.008. PMID: 25027067
Stockley RA, Miravitlles M, Vogelmeier C; Alpha One International Registry (A.I.R.).
Orphanet J Rare Dis 2013 Sep 24;8:149. doi: 10.1186/1750-1172-8-149. PMID: 24063809Free PMC Article

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