Challenging identification of a novel PiISF and the rare PiMmaltonZ α1-antitrypsin deficiency variants in two patients.
OBJECTIVE
α1-Antitrypsin (AAT) deficiency is associated with an increased risk for lung and liver disease. Identification of AAT deficiency as the underlying cause of these diseases is important in correct patient management.


METHODS
AAT deficiency is commonly diagnosed by demonstrating low concentrations of AAT followed by genotype and/or phenotype testing. However, this algorithm may miss novel AAT phenotypes.


RESULTS
We report two cases of AAT deficiency in two patients: a case of the novel phenotype PiISF, misclassified as PiII by phenotyping, and a case of the rare phenotype PiMmaltonZ misclassified as PiM2Z.


CONCLUSIONS
These cases highlight the importance of understanding the limitations of a commonly used diagnostic algorithm, use of further gene sequencing in applicable cases, and the potential for underdiagnosis of AAT deficiency in patients with chronic obstructive pulmonary disease.
Dept of Pathology, University of Utah School of Medicine, ARUP Laboratories, 500 Chipeta Way, Salt Lake City, UT 84108; david.grenache@path.utah.edu.
Brenda B
BB
Suh-Lailam
Melinda
M
Procter
Patti
P
Krautscheid
Jason
J
Haas
Shiva
S
Kumar
Rong
R
Mao
David G
DG
Grenache
D000328:Adult; D000465:Algorithms; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D029424:Pulmonary Disease, Chronic Obstructive / Q000175:diagnosis / Q000235:genetics*; D012306:Risk; D000515:alpha 1-Antitrypsin / Q000235:genetics*; D019896:alpha 1-Antitrypsin Deficiency / Q000175:diagnosis / Q000235:genetics*
D000515:alpha 1-Antitrypsin
AAT; Genotype; Mmalton; Phenotype; α1-Antitrypsin deficiency