alpha-1 antitrypsin deficiency
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Introduction
There are at least 50 inherited variants of alpha-1 antitrypsin. Severe inherited deficiency seen most often as the PiZZ & SZ phenotypes is associated with liver disease, especially in childhood [neonatal hepatitis syndrome & infantile cirrhosis] & with chronic lung disease in adults [[[A12923|emphysema]] & bronchitis].
Epidemiology
- 1/500 births in Sweden
- prevalence of PiZZ is US is 1:1670 to 1:3000
Pathology
- deficiency in SERPINA1 results in excessive neutrophil elastase resulting in destruction of elastin & diminished recoil in lung
- the effect is panacinar pulmonary emphysema
- some patients also develop liver disease &/or skin pathology[3][8]
- intrahepatic accumulation of variant protein inclusions may lead to cirrhosis[3]
Genetics
- autosomal co-dominant
- associated with defects in SERPINA1
- phenotyping: (Pi typing, Pi stands for Protease inhibitor)
- PiMM (normal)
- PiMZ (heterozygote)
- PiZZ (homozygote)
- accumulation of alpha-1 antitrypsin in rough endoplasmic reticulum & in PAS+ globules
- > 90% show evidence of lung disease
- Pi[null] - make no alpha-1 antitrypsin at all
Clinical manifestations
- signs & symptoms generally appear during the 3rd or 4th decade of life, but may appear in early childhood
- early & severe pulmonary emphysema
- basilar lung predominance of emphysema[3]
- nephrotic syndrome
- cholestatic hepatitis in the newborn
- cirrhosis (3%)
- necrotizing panniculitis[3]
- smoking hastens onset of emphysema
Laboratory
- serum protein electrophoresis
- alpha-1 antitrypsin normally accounts for 70% of alpha-1 band
- serum alpha-1 antitrypsin deficiency
- alpha-1 antitrypsin genotyping
- serum AST & serum ALT modestly increased
- serum alkaline phosphatase normal to modestly increased
- serum bilirubin normal
- see ARUP consult[7]
Radiology
basal (lower lobe) emphysema on chest X-ray
Complications
Differential diagnosis
Management
- stop smoking
- recombinant alpha-1 antitrypsin
- aerosols helpful for pulmonary symptoms, but not useful for liver disease
- IV administration may be appropriate for patients with homozygous alpha-1 antitrypsin deficiency
- liver transplantation is curative
- kidney transplantation
More general terms
- genetic syndrome (multisystem disorder)
- genetic disease of the lung
- genetic disease of the liver
- cirrhosis
Additional terms
- alpha-1-antitrypsin; alpha-1 protease inhibitor; alpha-1-antiproteinase; Serpin A1 (SERPINA1, AAT, PI, PRO0684, PRO2209)
- SERPINA1 gene mutation; alpha-1 antitrypsin gene mutation
References
- ↑ Harrison's Principles of Internal Medicine, 14th ed. Fauci et al (eds), McGraw-Hill Inc. NY, 1998, pg 1452
- ↑ Mayo Internal Medicine Board Review, 1998-99, Prakash UBS (ed) Lippincott-Raven, Philadelphia, 1998, pg 740
- ↑ 3.0 3.1 3.2 3.3 3.4 Medical Knowledge Self Assessment Program (MKSAP) 14, 15, 16, 18, 19. American College of Physicians, Philadelphia 2006, 2009, 2012, 2018, 2021.
- ↑ MedlinePLus: Alpha-1 Antitrypsin Deficiency https://medlineplus.gov/alpha1antitrypsindeficiency.html
- ↑ Genetics Home Reference: Alpha-1 antitrypsin deficiency https://ghr.nlm.nih.gov/condition/alpha-1-antitrypsin-deficiency
- ↑ OMIM https://mirror.omim.org/entry/613490
- ↑ 7.0 7.1 ARUP Consult: Alpha-1-Antitrypsin Deficiency - AAT The Physician's Guide to Laboratory Test Selection & Interpretation https://www.arupconsult.com/content/alpha-1-antitrypsin-deficiency
- ↑ 8.0 8.1 Silverman EK, Sandhaus RA. Clinical practice. Alpha1-antitrypsin deficiency. N Engl J Med. 2009 Jun 25;360(26):2749-57 PMID: https://www.ncbi.nlm.nih.gov/pubmed/19553648
- ↑ American Thoracic Society; European Respiratory Society. American Thoracic Society/European Respiratory Society statement: standards for the diagnosis and management of individuals with alpha-1 antitrypsin deficiency. Am J Respir Crit Care Med. 2003 Oct 1;168(7):818-900. PMID: https://www.ncbi.nlm.nih.gov/pubmed/14522813
Patient information
alpha-1 antitrypsin deficiency patient information