Alpha-1-Antitrypsin Deficiency

 
Alpha-1-antitrypsin is a glycoprotein produced primarily in the liver secreted under the influence of proinflammatory cytokines forming several globulins whose roles are to suppress additional tissue damage by neutralizing granulocyte elastase and proteinase primarily in the lung during infective and inflammatory process. Is responsible for protecting tissues against proteolytic damage by enzymes like neutrophil elastase and proteinase. It is also a tissue reparation inductor. Deficiency of alpha-1-antitrypsin (A1ATD) is a rare autosomal recessive co-dominant disorder most often seen in Northern European ancestry populations. A1ATD is the most common genetic cause of pediatric liver disease and transplantation. The defect in alpha-1-antitrypsin expression in the hepatocyte is followed by damage to the liver and/or lungs primarily. A1ATD can be asymptomatic or long-lasting and even permanently symptomatic depending in expression on the genotype and numerous exogenous factors such as infection, toxic or other damages to the liver and lungs. Liver damage occurs due to intrahepatocyte retention of alpha-1-antitrypsin and in the lung due to the lack of its protective effect. Early in life A1ATD causes a cholestatic syndrome, conjugated hyperbilirubinemia beyond the second week of life, associated with low birth weight and poor weight gain sometimes difficult to differentiate from biliary atresia. The liver damage is severe in only 1-2% of affected patients, most often has a slowly progressive character and juvenile cirrhosis develops in 15% of cases. In other organs A1ATD can cause pulmonary emphysema (chronic obstructive pulmonary disease), cytoplasmic anti-neutrophil cytoplasmic vasculitis and inflammatory necrotizing panniculitis in the skin. A1ATD individuals screened at birth who smoke develop COPD by age of 40 years. A1ATD is also associated with other diseases such as rheumatoid arthritis, sinusitis, nasal polyps, inflammatory bowel disease, peptic ulcer disease and diabetes. Management of A1ATD is limited. A diagnosis of A1ATD may have important implications including testing of family members, genetic counseling, smoking avoidance, avoidance of high risk occupations and consideration of augmentation therapy.

References:
1- Radlovic N, Lekovic Z, Radlovic V, Simic D, Topic A, Ristic D, Ducic S, Baletic A: Alpha-1-antitrypsin deficiency in children: clinical characteristics and diagnosis. Srp Arh Celok Lek. 142(9-10):547-50, 2014
2- Greulich T, Nell C, Hohmann D, Grebe M, Janciauskiene S, Koczulla AR, Vogelmeier CF: The prevalence of diagnosed alpha-1-antitrypsin deficiency and its comorbidities: results from a large population-based database. Eur Respir J. 2017 Jan 4;49(1). pii: 1600154. doi: 10.1183/13993003.00154-2016. Print 2017 Jan.
3- Aboussouan LS, Stoller JK: Detection of alpha-1 antitrypsin deficiency: a review. Respir Med. 103(3):335-41, 2009
4- Piitulainen E, Mostafavi B, Tanash HA: Health status and lung function in the Swedish alpha 1-antitrypsin deficient cohort, identified by neonatal screening, at the age of 37-40 years. Int J Chron Obstruct Pulmon Dis. 12:495-500, 2017
5- Khan Z, Venkat VL, Soltys KA, Stolz DB, Ranganathan S: A Challenging Case of Severe Infantile Cholestasis in Alpha-1 Antitrypsin Deficiency. Pediatr Dev Pathol. 20(2):176-181, 2017
6- Fregonese L, Stolk J: Hereditary alpha-1-antitrypsin deficiency and its clinical consequences. Orphanet J Rare Dis. 2008 Jun 19;3:16. doi: 10.1186/1750-1172-3-16.
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