Table 3. Methods of diagnosis for alpha-1 antitrypsin deficiency (AATD).

Test	Advantages	Disadvantages	References
Serum AAT tests
Nephelometry	Good reliability Inexpensive Standard method	Does not reliably detect heterozygotes	28,33
Radial immunodiffusion	Inexpensive None above nephelometry	Overestimates the concentration of AAT Inaccurate; not in use	28,33
Rocket electrophoresis	Inexpensive None above nephelometry	Inaccuracy and low sensitivity; not in use	28,33
Phenotyping and genotyping
Point of care detection of serum Z protein (Alphakit Quickscreen)	Detects Z allele homozygotes or heterozygotes Exclusion of non-Z AATD in primary care and in the overall chronic obstructive pulmonary disease population, with low pre-test probability Widely available and easy to interpret Small samples needed Cost-effective	Low negative predictive values in a population with a very high pre-test probability False negatives in PiMZ samples	31,33
Isoelectric focusing (IEF) method	Detects S and Z alleles and rare variants (F, I, and P) Identifies heterozygotes Highly specific and rapid Simple to perform Useful in screening programs	Null (Q0) mutations or M-like alleles are not detectable Interpretation of rare alleles can be difficult No longer regarded as standard for phenotyping	33
PCR-based tests	Detects the Mmalton allele Molecular diagnosis of S and Z allele	Null (or Q0) mutations are not detectable Requires specific primers for each allele	33
Luminex technology	Detects 14 AATD mutations simultaneously Short time to conduct testing Cost-effective Detects abnormalities across the entire genome using less DNA	Requires sophisticated bioinformatics systems to analyze and clinically interpret the data	32,33
Gene sequencing
Sanger method	Detects mutations caused by a variety of different mechanisms, including deletions, insertions, point mutations (silent, nonsense, and missense), and frameshift mutations Permits sequencing of introns	Can be expensive Not available in every hospital Requires sophisticated bioinformatics systems to analyze and clinically interpret the data	34