Genetic epidemiology of alpha‐1 antitrypsin deficiency in North America and Australia/New Zealand: Australia, Canada, New Zealand and the United States of America

Abstract

Alpha-1-antitrypsin deficiency (AAT deficiency) is one of the most common serious hereditary disorders in the world, as its affects all major racial subgroups worldwide, and there are an estimated 120.5 million carriers and deficient subjects worldwide. This genetic disease is related to susceptibility for development of jaundice in infants, liver disease in children and adults and pulmonary emphysema in adults. Moreover, AAT deficiency carrier phenotypes (PiMS and PiMZ) and deficiency allele phenotypes (PiSS, PiSZ and PiZZ) are suspected to predispose subjects to a variety of other adverse health effects. Because there is a limited database on the number of individuals affected by this disease worldwide, we have collected data on control cohorts in genetic epidemiological studies published on case-control studies in the peer-reviewed literature worldwide. Based on these data, we estimated the numbers of carriers and deficiency allele combinations for the two most common defective alleles, namely PiS and PiZ in 58 countries worldwide. The present paper focuses on the distribution of the PiS and PiZ deficiency alleles in Australia, Canada, New Zealand and the United States of America. A total of 31,042,232 individuals at risk for adverse health effects have been calculated in these four countries: 2,144,158 in Australia, 3,258,564 in Canada, 430,922 in New Zealand and 24,909,548 in the United States of America. The prevalences for all five phenotypic classes of AAT deficiency in each of these countries is as follows: Australia 1 out of 8.9, Canada 1 out of 9.8, New Zealand 1 out of 8.5 and the United States of America 1 out of 11.3. The geographical distribution of individual control cohorts and estimates of the numbers of carriers and deficiency allele phenotypes in each of these four countries are given in individual tables.

The Impact of Smoke Exposure on the Clinical Phenotype of Alpha-1 Antitrypsin Deficiency in Ireland: Exploiting a National Registry to Understand a Rare Disease

“…The gene frequency for the Z protein is most prevalent in northern and western European countries with severe deficiency (PiZZ) affecting up to 1:1500 (2), though it is less common in countries of predominantly Western European descent such as regions of North America and the Antipodes (11,12). In Ireland 1:2104 individuals are PiZZ homozygotes, though in our targeted detection program 1:71 tested were PiZZ homozygotes highlighting the effectiveness of the targeted detection approach (5).…”

Lung deposition of inhaled 1-proteinase inhibitor in cystic fibrosis and 1-antitrypsin deficiency

“…Approximately one in every 2,000-2,500 people born in Europe and North America is affected by these diseases [1,2]. In patients with CF, the submucosal bronchial glands are hypertrophied, and primary viscid secretions are frequently infected.…”

α1 Antitrypsin deficiency: current best practice in testing and augmentation therapy

“…In the USA and Europe it is estimated that approximately 1 of 4700 individuals in the general population are homozygous for the Z mutation, the most common mutation associated with severe deficiency [De Serres et al 2003a, 2003bAmerican Thoracic Society/European Respiratory Society, 2003]. The prevalence increases as testing is targeted towards more specific high-risk groups.…”