Alpha-1 antitrypsin deficiency: A conformational disease associated with lung and liver manifestations

被引：46

作者：

Greene, C. M. ^{[1
]}

Miller, S. D. W. ^{[1
]}

Carroll, T. ^{[1
]}

McLean, C. ^{[1
]}

O'Mahony, M. ^{[1
]}

Lawless, M. W. ^{[1
,2
]}

O'Neill, S. J. ^{[1
]}

Taggart, C. C. ^{[1
,3
]}

McElvaney, N. G. ^{[1
]}

机构：

[1] Royal Coll Surgeons Ireland, Educ & Res Ctr, Beaumont Hosp, Dept Med,Resp Res Div, Dublin 9, Ireland

[2] St James Hosp, Trinity Coll, Inst Mol Med, Hepatol Res Div, Dublin 8, Ireland

[3] Queens Univ Belfast, Sch Med & Dent, Belfast BT7 1NN, Antrim, North Ireland

来源：

JOURNAL OF INHERITED METABOLIC DISEASE | 2008年 / 31卷 / 01期

关键词：

D O I：

10.1007/s10545-007-0748-y

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Alpha-1 antitrypsin (A1AT) is a serine antiprotease produced chiefly by the liver. A1AT deficiency is a genetic disorder characterized by serum levels of less than 11 mu mol/L and is associated with liver and lung manifestations. The liver disease, which occurs in up to 15% of A1AT-deficient individuals, is a result of toxic gain-of-function mutations in the A1AT gene, which cause the A1AT protein to fold aberrantly and accumulate in the endoplasmic reticulum of hepatocytes. The lung disease is associated with loss-of-function, specifically decreased anti-protease protection on the airway epithelial surface. The so-called 'Z' mutation in A1AT deficiency encodes a glutamic acid-to-lysine substitution at position 342 in A1AT and is the most common A1AT allele associated with disease. Here we review the current understanding of the molecular pathogenesis of A1AT deficiency and the best clinical management protocols.

引用

页码：21 / 34

页数：14

共 111 条

[1] Enhanced phenotypic expression of alpha-1-antitrypsin deficiency in an MZ heterozygote with chronic hepatitis C [J].