Alpha-1 antitrypsin deficiency is not a rare disease but a disease that is rarely diagnosed.

Abstract

Articles in the literature on alpha-1 antitrypsin (AAT) deficiency have been interpreted as indicating that AAT deficiency is a rare disease that affects mainly Caucasians (whites) from northern Europe. In a recent publication on the worldwide racial and ethnic distribution of AAT deficiency, new data were presented demonstrating that it is also found in various populations of African blacks; Arabs and Jews in the Middle East; and Central, Far East, and Southeast Asians, as well as whites in Australia, Europe, New Zealand, and North America. The new data on the prevalence of AAT deficiency in other major racial groups worldwide will affect the standards for the diagnosis of AAT deficiency by the medical community, with the realization that is not a rare disease of whites in northern Europe and immigrants from these countries in the New World. In a total population of 4.4 billion in the 58 countries surveyed, there are at least 116 million carriers (those with Pi phenotypes PiMS and PiMZ) and 3.4 million with deficiency allele combinations (phenotypes PiSS, PiSZ, and PiZZ) for the two most prevalent deficiency alleles PiS and PiZ; therefore, the new data suggest that AAT deficiency may be one of the most common serious single-locus genetic diseases in the world. Particularly important is the unique susceptibility of AAT-deficient individuals to exposure to chemical and particulate environmental agents. Such exposures are known to result in both lung and liver disease as well as other adverse health effects.

The IDDEA project: a strategy for the detection of alpha-1 antitrypsin deficiency in COPD patients in the primary care setting

“…As a consequence, only a fraction of synthesized AAT is released into the circulation. The S allele (Pi*S) is more common than Pi*Z in some countries such as Spain and Portugal and its de Serres, 2003] and delayed diagnosis is common [Campbell, 2000].…”

Tempting Liver Fibrosis? Long-Term Psoriatic Methotrexate Therapy and Heterozygous α₁-Antitrypsin Deficiency

“…A1AT deficiency, an autosomal recessive endoplasmic reticulum disorder [23, 24], is one of the commonest single locus hereditary disorders in Caucasians [25, 26] and also probably worldwide [27]. It is associated with the inheritance of two protease inhibitor (Pi) deficiency alleles from the A1AT gene locus (chromosome 14q32.1) [26]; histologically, liver biopsies from these show acinar zone 1 A1AT globules detectable by PAS-diastase or, more reliably, by immunohistochemistry [28].…”

Recent Advances in the Research and Development of Alpha-1 Proteinase Inhibitor for Therapeutic Use

“…However, according to several publications, 1 -PI deficiency is widely under-and mis-diagnosed (e.g., de Serres, 2003;Bals et al, 2007 (Juvelekian & Stoller, 2004;Sandhaus, 2009). However, the ability of 1 -PI augmentation therapy to reduce the progression of emphysema still remains to be proven.…”