United States Targeted Detection Program for Alpha-1 Antitrypsin Deficiency

Alpha-1 antitrypsin deficiency (AATD) is an underdiagnosed genetic disorder that manifests primarily through pulmonary and hepatic impairment. In Romania, a targeted detection program testing for AATD was implemented between October 2012 and October 2016. A cohort study enrolled all patients with indication for AATD screening (lung or liver disease, adults and children, index and non-index cases). Testing methods were mainly represented by isoelectric focusing, genotyping and/or sequencing. 620 patients (21 children) were tested (median age 50.0�16.4 years, 58.1% men), 91.9% of proved normal. A total of 50 patients were identified to be carrying a modified genotype (26 men). Hardy-Weinberg equilibrium was used for assessing the frequency of the genetic abnormalities: 1/1.08 PiMM, 1/32 PiMS, 1/28 PiMZ, 1/48 M-rare allele heterozygote, 1/3906 PiSS, 1/2770 PiZZ, 1/1000 PiSZ and 1/12346 for a Z-rare allele heterozygote. Severe AATD was present with a 1% frequency. Prevalence of abnormal genotypes estimated for each at risk category was greater in neonate hepatitis (100%), bronchitis (20%) and adult liver cirrhosis (33.3%). In conclusion, a targeted AATD detection program with this formula is feasible in Romania and will be continued with the implementation of a national registry.

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PRS18 ANALYSIS OF PULMONARY-RELATED CLINICAL MANIFESTATIONS AND HEALTHCARE RESOURCE USE IN PATIENTS IN THE UNITED STATES WITH ALPHA-1 ANTITRYPSIN DEFICIENCY

Value in Health ◽

10.1016/j.jval.2020.04.1343 ◽

2020 ◽

Vol 23 ◽

pp. S352

Author(s):

E. Mayen Herrera ◽

C. Joseph ◽

M. Czorniak

Keyword(s):

United States ◽

Resource Use ◽

Healthcare Resource ◽

Clinical Manifestations ◽

The United States ◽

Healthcare Resource Use ◽

Antitrypsin Deficiency ◽

Alpha 1 Antitrypsin Deficiency ◽

Alpha 1 Antitrypsin

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Unique Case of Alpha 1-Antitrypsin Deficiency Causing Decreased Protein-C and S Activity Leading to DVT and Pulmonary Embolism

Edelweiss Applied Science and Technology ◽

10.33805/2576-8484.144 ◽

2018 ◽

pp. 232-233

Author(s):

Manoj Singla

Keyword(s):

United States ◽

Pulmonary Embolism ◽

Liver Disease ◽

Protein C ◽

The United States ◽

Unique Case ◽

Severe Deficiency ◽

Antitrypsin Deficiency ◽

Alpha 1 Antitrypsin Deficiency ◽

Alpha 1 Antitrypsin

Although Alpha-1 Antitrypsin Deficiency (AATD) is generally considered to be rare, estimates that 80,000 to 100,000 individuals in the United States have severe deficiency of AAT suggest that the disease is under-recognized. The prevalence of AAT varies considerably from one country to another; however, it is estimated that more than 3 million people worldwide have allele combinations associated with severe deficiency of AAT The pathogenesis of the liver disease is quite different and is called a "toxic gain of function." The liver disease results from the accumulation within the hepatocyte of unsecreted variant AAT protein. Only those genotypes associated with pathologic polymerization of AAT within the endoplasmic reticulum of hepatocytes (eg, PI*ZZ type AATD) produce disease. Most patients with liver disease due to AATD are homozygous for the Z allele (ie, PI*ZZ); liver disease does not occur in null homozygotes who have severe deficiency of AAT, but no intra-hepatocytic accumulation.

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