464:
653:
524:
632:-resistant inclusions within hepatocytes. Unlike glycogen and other mucins which are diastase sensitive (i.e., diastase treatment disables PAS staining), A1AT deficient hepatocytes will stain with PAS even after diastase treatment - a state thus referred to as "diastase resistant". The accumulation of these inclusions or globules is the main cause of liver injury in A1AT deficiency. However, not all individuals with PiZZ genotype develop liver disease (
645:
871:
620:(a physical process where a protein chain achieves its final conformation). 85 percent of the mutant Z form are unable to be secreted and remain in the hepatocyte. Nearly all liver disease caused by A1AT is due to the PiZZ genotype, although other genotypes involving different combinations of mutated alleles (compound heterozygotes) may also result in liver disease. A
830:
replacement therapy are not available. It is currently recommended that patients begin augmentation therapy only after the onset of emphysema symptoms. As of 2015 there were four IV augmentation therapy manufacturers in the United States, Canada, and several
European countries. IV therapies are the standard mode of augmentation therapy delivery.
897:
Another study detected a frequency of 1 in 1550 individuals. The highest prevalence of the PiZZ variant was recorded in the northern and western
European countries with mean gene frequency of 0.0140. Worldwide, an estimated 1.1 million people have A1AT deficiency and roughly 116 million are carriers
607:
With A1AT deficiency, the pathogenesis of the lung disease is different from that of the liver disease, which is caused by the accumulation of abnormal A1AT proteins in the liver, resulting in liver damage. As such, lung disease and liver disease of A1AT deficiency appear unrelated, and the presence
732:
with two different copies of the gene may have two different bands showing on electrofocusing, although a heterozygote with one null mutant that abolishes expression of the gene will only show one band. In blood test results, the IEF results are notated as, e.g., PiMM, where Pi stands for protease
691:
or necrotizing panniculitis. American guidelines recommend that all people with COPD are tested, whereas
British guidelines recommend this only in people who develop COPD at a young age with a limited smoking history or with a family history. The initial test performed is serum A1AT level. A low
829:
People with lung disease due to A1AD may receive intravenous infusions of alpha-1 antitrypsin, derived from donated human plasma. This augmentation therapy is thought to arrest the course of the disease and halt any further damage to the lungs. Long-term studies of the effectiveness of A1AT
1141:
Marciniuk, DD; Hernandez, P; Balter, M; Bourbeau, J; Chapman, KR; Ford, GT; Lauzon, JL; Maltais, F; O'Donnell, DE; Goodridge, D; Strange, C; Cave, AJ; Curren, K; Muthuri, S; Canadian
Thoracic Society COPD Clinical Assembly Alpha-1 Antitrypsin Deficiency Expert Working, Group (2012).
678:
A1AT deficiency remains undiagnosed in many patients. Patients are usually labeled as having COPD without an underlying cause. It is estimated that about 1% of all COPD patients actually have an A1AT deficiency. Testing is recommended in those with COPD, unexplained
854:(NSAIDs) should also be avoided, as these medications may worsen liver disease in general, and may particularly accelerate the liver injury associated with A1AD. Augmentation therapy is not appropriate for people with liver disease. If progressive
557:, a neutral serine protease that controls lung elastolytic activity which stimulates mucus secretion and CXCL8 release from epithelial cells that perpetuate the inflammatory state. With A1AT deficiency, neutrophil elastase can disrupt
727:
has exceeded the number of letters in the alphabet, subscripts have been added to most recent discoveries in this area, as in the
Pittsburgh mutation described above. As every person has two copies of the A1AT gene, a
833:
Liver disease due to A1AD does not include any specific treatment, beyond routine care for chronic liver disease. However, the presence of cirrhosis affects treatment in several ways. Individuals with cirrhosis and
2110:
2095:
2080:
715:
or charge in a pH gradient. Normal A1AT is termed M, as it migrates toward the center of such an IEF gel. Other variants are less functional and are termed A-L and N-Z, dependent on whether they run
527:
Photomicrograph of a liver biopsy from a patient with alpha-1 antitrypsin deficiency. The PAS with diastase stain shows the diastase-resistant pink globules that are characteristic of this disease.
467:
Conditions associated with alpha-1 antitrypsin deficiency, occurring due to paucity of AAT in circulation allowing uninhibited inflammation in lungs, and accumulation of mutated AAT in the liver
636:), despite the presence of accumulated mutated protein in the liver. Therefore, additional factors (environmental, genetic, etc.) likely influence whether liver disease develops.
515:
mutation at position 342 (dbSNP: rs28929474), while PiS is caused by a glutamic acid to valine mutation at position 264 (dbSNP: rs17580). Other rarer forms have been described .
699:
does not completely distinguish between A1AT and other minor proteins at the alpha-1 position (agarose gel), antitrypsin can be more directly and specifically measured using a
448:
followed by prolonged jaundice. Between 3% and 5% of children with ZZ mutations develop life-threatening liver disease, including liver failure. A1AD is a leading reason for
2026:
De Soyza, J; Pye, A; Turner, AM (December 2023). "Are clinical trials into emerging drugs for the treatment of alpha-1 antitrypsin deficiency providing promising results?".
1399:
Sandhaus, Robert A.; Turino, Gerard; Brantly, Mark L.; Campos, Michael; Cross, Carroll E.; Goodman, Kenneth; Hogarth, D. Kyle; Knight, Shandra L.; Stocks, James M. (2016).
57:
667:
in the lower lobes of a subject with type ZZ alpha-1 antitrypsin deficiency. There is also increased lung density in areas with compression of lung tissue by the bullae.
507:
gene have been identified, many with clinically significant effects. The most common cause of severe deficiency, PiZ, is a single base-pair substitution leading to a
1287:
568:
Normal blood levels of alpha-1 antitrypsin may vary with analytical method but are typically around 1.0-2.7 g/L. In individuals with PiSS, PiMZ and PiSZ
1999:
Sharp H, Bridges R, Krivit W, Freier E (1969). "Cirrhosis associated with alpha-1-antitrypsin deficiency: a previously unrecognized inherited disorder".
744:. Alpha-1 antitrypsin levels in the blood depend on the genotype. Some mutant forms fail to fold properly and are, thus, targeted for destruction in the
1276:
1815:
576:
in people who do not smoke. However, in individuals with the PiZZ genotype, A1AT levels are less than 15% of normal, and they are likely to develop
707:
method. Thus, protein electrophoresis is useful for screening and identifying individuals likely to have a deficiency. A1AT is further analyzed by
692:
level of A1AT confirms the diagnosis and further assessment with A1AT protein phenotyping and A1AT genotyping should be carried out subsequently.
401:
it is uncommon. About 3% of people with COPD are believed to have the condition. Alpha-1 antitrypsin deficiency was first described in the 1960s.
1206:
723:
to the M band. The presence of deviant bands on IEF can signify the presence of alpha-1 antitrypsin deficiency. Since the number of identified
572:, blood levels of A1AT are reduced to between 40 and 60% of normal levels; this is usually sufficient to protect the lungs from the effects of
17:
616:, because the A1AT is not secreted properly and therefore accumulates in the liver. The mutant Z form of A1AT protein undergoes inefficient
671:
The gold standard of diagnosis for A1AD consists of blood tests to determine the phenotype of the AAT protein or genotype analysis of DNA.
1144:"Alpha-1 antitrypsin deficiency targeted testing and augmentation therapy: a Canadian Thoracic Society clinical practice guideline"
1839:"Intravenous alpha-1 antitrypsin augmentation therapy for treating patients with alpha-1 antitrypsin deficiency and lung disease"
28:
720:
716:
394:
is also recommended. Life expectancy among those who smoke is 50 years while among those who do not smoke it is almost normal.
608:
of one does not appear to predict the presence of the other. Between 10 and 15% of people with the PiZZ genotype will develop
1259:
414:
301:
117:
901:
A1AD is one of the most common genetic diseases worldwide and the second most common metabolic disease affecting the liver.
347:
tends to result in milder disease than two defective alleles. The diagnosis is suspected based on symptoms and confirmed by
565:
that can develop into chronic bronchitis. Both conditions are the makeup of chronic obstructive pulmonary disease (COPD).
2125:
737:
1972:
Laurell CB, Eriksson S (1963). "The electrophoretic alpha1-globulin pattern of serum in alpha1-antitrypsin deficiency".
1692:
1956:
851:
917:
in Sweden. Laurell, along with a medical resident, Sten
Eriksson, made the discovery after noting the absence of the α
483:
in which inflammation of the blood vessels may affect a number of organs but predominantly the lungs and the kidneys.
1625:
1231:
1087:
1541:"Phospholipid transfer protein and alpha-1 antitrypsin regulate Hck kinase activity during neutrophil degranulation"
397:
The condition affects about 1 in 2,500 people of
European descent. Severe deficiency occurs in about 1 in 5,000. In
1720:"Reference and Interpretive Ranges for α1-Antitrypsin Quantitation by Phenotype in Adult and Pediatric Populations"
688:
480:
1949:
Sleisenger and
Fordtran's Gastrointestinal and Liver Disease- 2 Volume Set: Pathophysiology, Diagnosis, Management
1047:
675:
is the gold standard for determining the extent of hepatic fibrosis and assessing for the presence of cirrhosis.
440:
A1AD may cause several manifestations associated with liver disease, which include impaired liver function and
580:
at a young age. Cigarette smoke is especially harmful to individuals with A1AD. In addition to increasing the
1643:"Role of elastases in the pathogenesis of chronic obstructive pulmonary disease: Implications for treatment"
1291:
463:
925:
in five of 1500 samples; three of the five patients were found to have developed emphysema at a young age.
1605:
1768:"Systematic review: the natural history of alpha-1 antitrypsin deficiency, and associated liver disease"
2238:
2223:
1284:
Global
Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Pulmonary Disease
785:
1351:
Patel, Dhiren; Teckman, Jeffrey H. (November 2018). "Alpha-1-Antitrypsin
Deficiency Liver Disease".
2136:
994:
2248:
2243:
1076:
Stradling, John; Stanton, Andrew; Rahman, Najib M.; Nickol, Annabel H.; Davies, Helen E. (2010).
696:
112:
652:
452:
in newborns. In newborns and children, A1AD may cause jaundice, poor feeding, poor weight gain,
879:
664:
191:
162:
2176:
1199:
1077:
523:
2198:
2089:
1221:
1187:
859:
811:
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633:
449:
379:
340:
1552:
819:
807:
803:
708:
577:
562:
387:
375:
371:
235:
8:
2253:
2114:
910:
847:
835:
656:
625:
554:
532:
496:
336:
324:
289:
288:. Onset of lung problems is typically between 20 and 50 years of age. This may result in
97:
65:
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1642:
1617:
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1540:
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92:
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1719:
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2008:
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1789:
1741:
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1621:
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383:
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125:
72:
1766:
Townsend, S.A; Edgar, R.G; Ellis, P.R; Kantas, D; Newsome, P.N; Turner, A.M (2018).
1590:
1380:
711:(IEF) in the pH range 4.5-5.5, where the protein migrates in a gel according to its
2035:
1981:
1951:(Eleventh ed.). Philadelphia, PA: Elsevier. 29 June 2020. pp. 1189–1192.
1920:
1912:
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1112:
795:
363:
277:
227:
211:
85:
2187:
2039:
1416:
2141:
1901:"Alpha1-antitrypsin deficiency. 1: epidemiology of alpha1-antitrypsin deficiency"
1103:
Clark, VC (May 2017). "Liver Transplantation in Alpha-1 Antitrypsin Deficiency".
922:
791:
741:
617:
418:
359:
328:
297:
248:
223:
207:
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and components of the alveolar wall of the lung that may lead to emphysema, and
1916:
1659:
1612:(second ed.). Basic Mechanisms and Clinical Management. pp. 737–749.
1564:
839:
684:
609:
2209:
2104:
1985:
1364:
1116:
886:
ancestry are at the highest risk for A1AD. Four percent of them carry the PiZ
2232:
2152:
1862:
1808:"Chronic obstructive pulmonary disease in over 16s: diagnosis and management"
1736:
1401:"The Diagnosis and Management of Alpha-1 Antitrypsin Deficiency in the Adult"
929:
855:
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508:
352:
285:
184:
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476:
457:
453:
313:
281:
129:
2012:
1525:
1466:
1160:
2204:
2171:
1807:
1490:"Multiple tissues express alpha 1-antitrypsin in transgenic mice and man"
799:
367:
348:
231:
180:
156:
77:
444:. In newborns, alpha-1 antitrypsin deficiency can result in early onset
2193:
891:
749:
745:
593:
550:
542:
218:
81:
2072:
1784:
1767:
1506:
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production. Symptoms may resemble recurrent respiratory infections or
2182:
823:
724:
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613:
597:
589:
441:
410:
391:
305:
243:
121:
1453:
Silverman EK, Sandhaus RA (2009). "Alpha1-Antitrypsin Deficiency".
944:
Recombinant and inhaled forms of A1AT treatment are being studied.
629:
573:
569:
546:
445:
382:
may be an option. Avoiding smoking is recommended. Vaccination for
320:
293:
148:
105:
101:
503:
has been localized to chromosome 14q32. Over 75 mutations of the
421:, though smoking greatly increases the risk. Symptoms may include
558:
422:
2130:
1140:
644:
2099:
2084:
1837:
Gøtzsche, Peter C.; Johansen, Helle Krogh (20 September 2016).
1223:
Alpha-1 Antitrypsin Deficiency: Clinical Aspects and Management
887:
601:
585:
512:
434:
430:
426:
398:
344:
196:
870:
814:
may be an option. Avoiding smoking and getting vaccinated for
588:, cigarette smoke directly inactivates alpha-1 antitrypsin by
538:
475:-antitrypsin deficiency has been associated with necrotizing
1699:. Mayo Foundation for Medical Education and Research (MFMER)
1075:
842:. All people with A1AD and cirrhosis should be screened for
810:
may also be recommended. In those with severe liver disease
378:
may also be recommended. In those with severe liver disease
1398:
417:
during their thirties or forties even without a history of
332:
733:
inhibitor and "MM" is the banding pattern of that person.
553:. In a healthy lung, it functions as an inhibitor against
1998:
1941:
1765:
756:. The serum levels of some of the common genotypes are:
27:"AATD" redirects here. For the US Army directorate, see
1539:
Ochieng, Pius; Nath, Sridesh; Macarulay, Reane (2018).
56:
1288:
Global Initiative for Chronic Obstructive Lung Disease
2062:
1538:
838:
should avoid contact sports to minimize the risk of
775:
PiZZ: 10–15% (severe alpha-1 antitrypsin deficiency)
1487:
1254:(7th ed.). Elsevier/Saunders. pp. 911–2.
1488:Carlson, J.A.; Rogers, B.B.; Sifers, R.N. (1988).
2025:
1898:
1816:National Institute for Health and Care Excellence
1452:
339:and buildup of abnormal A1AT in the liver. It is
2230:
1836:
1252:Robbins and Cotran Pathological Basis of Disease
1249:
936:described A1AD in the context of liver disease.
251:~50 years (smokers), nearly normal (non-smokers)
1971:
648:Emphysema due to alpha-1 antitrypsin deficiency
491:Serpin peptidase inhibitor, clade A, member 1 (
1640:
1346:
1344:
1342:
1340:
1338:
1336:
1334:
1332:
537:A1AT is a glycoprotein mainly produced in the
335:. The underlying mechanism involves unblocked
327:(A1AT). Risk factors for lung disease include
1718:Donato, Leslie; Jenkins; et al. (2012).
1717:
1330:
1328:
1326:
1324:
1322:
1320:
1318:
1316:
1314:
1312:
1219:
1079:Oxford Case Histories in Respiratory Medicine
1965:
1448:
1446:
1444:
1350:
932:was made six years later, when Harvey Sharp
471:Apart from COPD and chronic liver disease, α
1899:Luisetti, M; Seersholm, N (February 2004).
1894:
1892:
1890:
1843:The Cochrane Database of Systematic Reviews
1268:
2224:Alpha-1-antitrypsin deficiency on Orphanet
1992:
1772:Alimentary Pharmacology & Therapeutics
1309:
1250:Kumar V, Abbas AK, Fausto N, eds. (2005).
1042:
1040:
1038:
1036:
989:
987:
985:
983:
981:
979:
977:
541:by hepatocytes, and, in some quantity, by
55:
1924:
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1016:
975:
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967:
965:
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961:
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858:or decompensated cirrhosis develop, then
806:of the A1AT protein or in severe disease
374:of the A1AT protein or in severe disease
1887:
1205:CS1 maint: numeric names: authors list (
1071:
1069:
869:
651:
643:
522:
462:
772:PiSZ: 40% of normal serum level of A1AT
769:PiMZ: 60% of normal serum level of A1AT
766:PiSS: 60% of normal serum level of A1AT
763:PiMS: 80% of normal serum level of A1AT
736:Other detection methods include use of
495:) is the gene that encodes the protein
29:Aviation Applied Technology Directorate
14:
2231:
1724:American Journal of Clinical Pathology
1603:
1405:Chronic Obstructive Pulmonary Diseases
1274:
1240:
1131:
1013:
954:
790:Treatment of lung disease may include
786:Alpha-1 antitrypsin § Medical use
358:Treatment of lung disease may include
1394:
1392:
1390:
1102:
1066:
890:; between 1 in 625 and 1 in 2000 are
415:chronic obstructive pulmonary disease
404:
302:chronic obstructive pulmonary disease
1641:Demkow, U; Overveld, FJ van (2010).
1220:Köhnlein, Thomas; Welte, T. (2007).
748:, whereas others have a tendency to
852:Nonsteroidal antiinflammatory drugs
752:, thereafter being retained in the
738:enzyme-linked-immuno-sorbent-assays
24:
1618:10.1016/B978-0-12-374001-4.00061-4
1387:
518:
409:Individuals with A1AD may develop
25:
2265:
2058:
1226:. UNI-MED Verlag AG. p. 16.
425:(on exertion and later at rest),
319:A1AD is due to a mutation in the
2028:Expert Opinion on Emerging Drugs
1048:"Alpha-1 antitrypsin deficiency"
995:"alpha-1 antitrypsin deficiency"
689:granulomatosis with polyangiitis
481:granulomatosis with polyangiitis
323:gene that results in not enough
2019:
1830:
1800:
1759:
1711:
1685:
1634:
1606:"Chapter 61 - Future Therapies"
1597:
1532:
1481:
1455:New England Journal of Medicine
1290:. pp. 9–17. Archived from
909:A1AD was discovered in 1963 by
865:
604:activity by a factor of 2,000.
2199:Alpha-1 antitrypsin deficiency
1855:10.1002/14651858.CD007851.pub3
1213:
1096:
874:Distribution of PiZZ in Europe
798:, and, when infections occur,
366:, and, when infections occur,
266:Alpha-1 antitrypsin deficiency
42:Alpha-1 antitrypsin deficiency
18:Alpha 1-antitrypsin deficiency
13:
1:
2210:Alpha1-Antitrypsin Deficiency
2040:10.1080/14728214.2023.2296088
1417:10.15326/jcopdf.3.3.2015.0182
947:
343:, meaning that one defective
1148:Canadian Respiratory Journal
779:
639:
479:(a skin condition) and with
300:. Complications may include
7:
1082:. OUP Oxford. p. 129.
939:
486:
10:
2270:
1917:10.1136/thorax.2003.006494
1660:10.1186/2047-783x-15-s2-27
1565:10.1038/s41598-018-33851-8
1277:"Diagnosis and Assessment"
904:
783:
624:in such cases will reveal
530:
296:, or an increased risk of
26:
2162:
2066:
1986:10.1080/00365516309051324
1604:Barnes, Peter J. (2009).
1365:10.1016/j.cld.2018.06.010
1117:10.1016/j.cld.2016.12.008
255:
242:
217:
202:
190:
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155:
143:
135:
111:
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71:
63:
54:
50:α1-antitrypsin deficiency
46:
41:
1737:10.1309/AJCPMEEJK32ACYFP
1353:Clinics in Liver Disease
1105:Clinics in Liver Disease
1974:Scand J Clin Lab Invest
999:Genetics Home Reference
846:, and should avoid all
697:protein electrophoresis
563:hypersecretion of mucus
875:
668:
649:
600:forms, decreasing the
528:
468:
259:1 in 2,500 (Europeans)
192:Differential diagnosis
1467:10.1056/NEJMcp0900449
873:
860:liver transplantation
826:is also recommended.
812:liver transplantation
804:Intravenous infusions
754:endoplasmic reticulum
655:
647:
634:incomplete penetrance
526:
466:
450:liver transplantation
380:liver transplantation
372:Intravenous infusions
341:autosomal co-dominant
236:intravenous infusions
808:lung transplantation
740:in vitro and radial
709:isoelectric focusing
659:of the lung showing
578:panlobular emphysema
376:lung transplantation
1557:2018NatSR...815394O
1161:10.1155/2012/920918
911:Carl-Bertil Laurell
878:People of Northern
848:alcohol consumption
836:portal hypertension
760:PiMM: 100% (normal)
705:immunoturbidimetric
657:Computed tomography
555:neutrophil elastase
533:Alpha-1 antitrypsin
497:alpha-1 antitrypsin
423:shortness of breath
337:neutrophil elastase
325:alpha-1 antitrypsin
290:shortness of breath
280:that may result in
179:Based on symptoms,
98:Shortness of breath
66:Alpha-1 antitrypsin
2163:External resources
1653:(Suppl 2): 27–35.
1198:has generic name (
915:University of Lund
876:
862:may be necessary.
844:esophageal varices
669:
650:
529:
469:
405:Signs and symptoms
333:environmental dust
139:20 to 50 years old
2239:Diseases of liver
2219:
2218:
1785:10.1111/apt.14537
1507:10.1172/JCI113580
1461:(26): 2749–2757.
1275:Vestbo J (2013).
1261:978-0-7216-0187-8
713:isoelectric point
310:neonatal jaundice
263:
262:
175:Diagnostic method
126:neonatal jaundice
36:Medical condition
16:(Redirected from
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2016:
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1302:
1297:on 28 March 2016
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1044:
1011:
1010:
1008:
1006:
991:
921:band on protein
796:inhaled steroids
584:reaction in the
364:inhaled steroids
278:genetic disorder
228:inhaled steroids
212:liver transplant
147:Mutation in the
86:Medical genetics
59:
39:
38:
21:
2269:
2268:
2264:
2263:
2262:
2260:
2259:
2258:
2229:
2228:
2220:
2215:
2214:
2158:
2157:
2075:
2061:
2056:
2055:
2024:
2020:
1997:
1993:
1970:
1966:
1959:
1947:
1946:
1942:
1897:
1888:
1849:(9): CD007851.
1835:
1831:
1821:
1819:
1818:. December 2018
1812:www.nice.org.uk
1806:
1805:
1801:
1764:
1760:
1750:
1748:
1716:
1712:
1702:
1700:
1691:
1690:
1686:
1639:
1635:
1628:
1610:Asthma and COPD
1602:
1598:
1537:
1533:
1494:J. Clin. Invest
1486:
1482:
1451:
1442:
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1101:
1097:
1090:
1074:
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1055:
1046:
1045:
1014:
1004:
1002:
993:
992:
955:
950:
942:
923:electrophoresis
920:
907:
868:
792:bronchodilators
788:
782:
742:immunodiffusion
642:
618:protein folding
614:liver cirrhosis
535:
521:
519:Pathophysiology
489:
474:
407:
360:bronchodilators
329:tobacco smoking
298:lung infections
249:Life expectancy
238:of A1AT protein
224:Bronchodilators
208:lung transplant
37:
32:
23:
22:
15:
12:
11:
5:
2267:
2257:
2256:
2251:
2249:Lung disorders
2246:
2244:Serpinopathies
2241:
2227:
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2190:
2179:
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2071:
2070:
2068:
2067:Classification
2060:
2059:External links
2057:
2054:
2053:
2034:(4): 227–231.
2018:
2001:J Lab Clin Med
1991:
1980:(2): 132–140.
1964:
1958:978-0323609623
1957:
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1886:
1829:
1799:
1778:(7): 877–885.
1758:
1730:(3): 398–405.
1710:
1684:
1633:
1626:
1596:
1531:
1480:
1440:
1411:(3): 668–682.
1386:
1359:(4): 643–655.
1308:
1267:
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1196:|first15=
1130:
1111:(2): 355–365.
1095:
1088:
1065:
1012:
1001:. January 2013
952:
951:
949:
946:
941:
938:
928:The link with
918:
906:
903:
898:of mutations.
867:
864:
840:splenic injury
784:Main article:
781:
778:
777:
776:
773:
770:
767:
764:
761:
685:bronchiectasis
683:, unexplained
641:
638:
610:liver fibrosis
520:
517:
488:
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1647:Eur J Med Res
1644:
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1627:9780123740014
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1154:(2): 109–16.
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930:liver disease
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718:
714:
710:
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702:
701:nephelometric
698:
693:
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681:liver disease
676:
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509:glutamic acid
506:
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361:
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354:
353:genetic tests
350:
346:
342:
338:
334:
330:
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322:
317:
315:
311:
307:
303:
299:
295:
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286:liver disease
283:
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258:
254:
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247:
245:
241:
237:
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229:
225:
222:
220:
216:
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209:
206:Medications,
205:
201:
198:
195:
193:
189:
186:
185:genetic tests
182:
178:
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172:
168:
164:
160:
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154:
150:
146:
142:
138:
134:
131:
127:
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119:
116:
114:
113:Complications
110:
107:
103:
99:
96:
94:
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64:Structure of
62:
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2181:
2170:
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2135:
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2007:(6): 934–9.
2004:
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1994:
1977:
1973:
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1948:
1943:
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1908:
1904:
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1842:
1832:
1820:. Retrieved
1811:
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1749:. Retrieved
1727:
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1701:. Retrieved
1696:
1687:
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1497:
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1299:. Retrieved
1292:the original
1283:
1270:
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1188:cite journal
1151:
1147:
1108:
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1078:
1056:. Retrieved
1051:
1003:. Retrieved
998:
943:
933:
927:
908:
900:
896:
877:
866:Epidemiology
832:
828:
820:pneumococcus
789:
735:
730:heterozygote
694:
677:
673:Liver biopsy
670:
622:liver biopsy
606:
596:residues to
582:inflammatory
567:
536:
504:
500:
492:
490:
477:panniculitis
470:
458:splenomegaly
454:hepatomegaly
439:
408:
396:
388:pneumococcus
357:
318:
314:panniculitis
282:lung disease
273:
269:
265:
264:
157:Risk factors
130:panniculitis
33:
2205:GeneReviews
2172:MedlinePlus
1703:16 November
1697:Mayo Clinic
1693:"Emphysema"
1058:12 December
1005:12 December
800:antibiotics
628:-positive,
551:macrophages
543:enterocytes
368:antibiotics
349:blood tests
232:antibiotics
181:blood tests
136:Usual onset
78:Pulmonology
47:Other names
2254:Hepatology
2233:Categories
2194:Patient UK
2148:DiseasesDB
1751:17 January
948:References
892:homozygous
750:polymerize
746:proteasome
594:methionine
592:essential
531:See also:
219:Medication
82:Hepatology
2183:eMedicine
1863:1469-493X
1822:11 August
824:hepatitis
816:influenza
780:Treatment
725:mutations
661:emphysema
640:Diagnosis
598:sulfoxide
590:oxidizing
570:genotypes
547:monocytes
442:cirrhosis
411:emphysema
392:hepatitis
384:influenza
306:cirrhosis
256:Frequency
244:Prognosis
203:Treatment
161:Northern
122:cirrhosis
73:Specialty
2048:38112023
1935:14760160
1881:27644166
1794:29446109
1746:22912357
1679:21147616
1591:53017522
1583:30337619
1475:19553648
1435:28848891
1381:52883809
1373:30266154
1301:9 August
1180:22536580
1125:28364818
940:Research
880:European
717:proximal
630:diastase
574:elastase
505:SERPINA1
501:SERPINA1
493:SERPINA1
487:Genetics
446:jaundice
427:wheezing
321:SERPINA1
304:(COPD),
294:wheezing
169:ancestry
163:European
149:SERPINA1
102:wheezing
93:Symptoms
2188:med/108
2142:D019896
2013:4182334
1926:1746939
1872:6457738
1670:4360323
1574:6193999
1553:Bibcode
1526:3260605
1426:5556762
1171:3373286
913:at the
905:History
884:Iberian
586:airways
559:elastin
419:smoking
276:) is a
167:Iberian
2177:000120
2131:107400
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934:et al.
888:allele
822:, and
721:distal
665:bullae
602:enzyme
549:, and
513:lysine
435:asthma
431:sputum
429:, and
399:Asians
390:, and
345:allele
197:Asthma
144:Causes
2120:273.4
2105:E88.0
1587:S2CID
1377:S2CID
1295:(PDF)
1280:(PDF)
539:liver
413:, or
312:, or
2137:MeSH
2126:OMIM
2115:9-CM
2090:5C5A
2044:PMID
2009:PMID
1953:ISBN
1931:PMID
1877:PMID
1859:ISSN
1847:2016
1824:2019
1790:PMID
1753:2014
1742:PMID
1705:2021
1675:PMID
1622:ISBN
1579:PMID
1522:PMID
1471:PMID
1431:PMID
1369:PMID
1303:2019
1256:ISBN
1228:ISBN
1207:link
1200:help
1176:PMID
1121:PMID
1084:ISBN
1060:2017
1052:GARD
1007:2017
882:and
663:and
456:and
331:and
274:AATD
270:A1AD
165:and
151:gene
118:COPD
2153:434
2111:ICD
2096:ICD
2081:ICD
2036:doi
1982:doi
1921:PMC
1913:doi
1867:PMC
1851:doi
1780:doi
1732:doi
1728:138
1665:PMC
1655:doi
1614:doi
1569:PMC
1561:doi
1512:PMC
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