Alpha-1 antitrypsin deficiency (A1AD) is a rare hereditary disorder that most commonly manifests as chronic obstructive pulmonary disease (COPD) or liver disease. 

People with A1AD lack the enzyme alpha-1-antitrypsin (ATT), which offers a protective factor to lung and liver tissue. Progressive destruction to lung tissue leads to early-onset emphysema, which can be accelerated by smoking or inhaling toxic chemicals. A1AD has around 120 genotypes, all leading to varying severity of A1AD. The three most common alleles that lead to the deficiency of ATT are Pi*SS, Pi*SZ, and Pi*ZZ, although most clinical cases of A1AD are caused by the Pi*ZZ genotype. Individuals who present this genotype are described as being “high deficient” due to producing only 10–20% of the normal amount of serum ATT. It is widely accepted that A1AD arose from those of European descent, with this disorder thought to affect approximately 1 out of every 1,500–3,500 individuals of European ancestry.

GlobalData epidemiologists have shown the variations in the total prevalence of A1AD using the allele frequency (%) of Pi*ZZ in men and women of all ages across the 16 major markets (Figure 1). The highest allele frequency (%) was shown in the US and Spain, which both had an approximate Pi*ZZ allele frequency of 0.03%, followed by the UK with a frequency of 0.02%. The lowest frequencies were seen across the African and Asian markets, with South Africa and China showing a Pi*ZZ allele frequency of 0.00%.

The first recognised case of A1AD was described by Laurell and Eriksson in Sweden in 1963, and led people to believe that this disorder arose in European populations. High Pi*ZZ allele frequencies seen in countries across Europe supported this theory. High Pi*ZZ allele frequency shown in the US can be linked back to the early 19th century, where a large influx of European migrants was seen. Early migrant flows to the US were dominated by north-west European migrants, particularly from Scandinavia and the UK. Two-thirds of European migrants entered the US at this time, with large numbers also entering Canada, Australasia and Latin America.

The lowest allele frequency of Pi*ZZ was seen across African and Asian countries, with these populations having smaller concentrations of European migrants. A1AD is frequently underdiagnosed or misdiagnosed, and without worldwide standards for diagnosis, it is hard to compare prevalence across differing populations. The World Health Organization (WHO) has set a recommendation that every person diagnosed with COPD should be tested for ATT, but there is not as yet any testing in place for individuals with European ancestry.

Figure 1: Pi*ZZ allele frequency across the 16MM, men and women, all ages (%)

Source: GlobalData © GlobalData

16MM: the US, France, Germany, Italy, Spain, the UK, Japan, Australia, Brazil, Canada, China, India, Mexico, Russia, South Africa, and South Korea.

Related Reports: 

GlobalData (2019) Chronic Obstructive Pulmonary Disease: Epidemiology Forecasts to 2025, Epidemiology model, June 2017, GDHCER152-17

GlobalData (2019) Cystic Fibrosis: Epidemiology Forecast to 2028, Epidemiology model, March 2019, GDHCER147-17

GlobalData (2019) Parkinson’s Disease: Epidemiology Forecast to 2026, Epidemiology model, May 2018, GDHCER183-18