Naslov
Alpha1-antitrypsin deficiency confirmed by quantification and phenotyping (PI*ZZ) in discrepancy with genotyping results(M/Z)

Autori
Štefanović, Mario ; Tešija Kuna, Andrea ; Vukasović, Ines ; Vrkić, Nada

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
Clinical chemistry and laboratory medicine / Plebani, Mario - Berlin : Walter de Gruyter, 2014, S839-S839

Skup
IFCC WorldLab Istanbul 2014

Mjesto i datum
Istanbul, Turska, 22.06.2014. - 26.06.2014

Vrsta sudjelovanja
Poster

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
Alpha1-antitrypsin; Allele; Genotyping; Phenotyping; Sequencing

Sažetak
BACKGROUND: Alpha1-antitrypsin (A1AT) is a plasmatic glycoprotein, primary inhibitor of the serine protease leukocyte elastase. It is highly polymorphic protein, and some variations within A1AT gene are associated with decreased serum concentrations or dysfunctional protein, causing A1AT deficiency. Besides common M allele, there are two most common disease associated alleles: Pi*S and Pi*Z. Patients with homozygous or compound heterozygous combination of Pi*S (codon E288V) or/and Pi*Z (codon E366K) alleles have low or insufficient A1AT concentration. That increases the risk for uncontrolled proteolytic damage in lower respiratory tract and developing chronic obstructive respiratory disease, or in the case of Z allele, of liver damage caused by inclusions of polymerized protein. METHODS: Methods used in our laboratory are in concordance with common laboratory procedure testing for A1AT deficiency and involves quantification of protein (immunoturbidimetry), genotyping (realtime PCR - melting curve analysis, LightCycler, Roche, Switzerland) of most common Pi*S and Pi*Z alleles and confirmation by phenotyping (semi-automated method of isoelectric focusing with immunofixation, Sebia, France). Here we present male patient, 42 years old, with symptoms of chronic obstructive respiratory disease for whom laboratory testing for suspected A1AT deficiency was requested. A1AT serum concentration (0.14 g/L) corresponded to determined PiZZ phenotype, but both was in discordance with genotyping results (Pi*S: M/M and Pi*Z: M/Z). RESULTS: All results were confirmed on repeated testing. This discrepancy between A1AT concentration, genotype, and phenotype could be consistent with the presence of a Z allele and a null allele (Z/null) that would not be detected by either phenotyping or genotyping. Determined PiZZ phenotype, however, is clinically more compatible with the low A1AT concentration and observed clinical symptoms than M/Z genotype. CONCLUSIONS: We concluded this case as genotyping method inability to detect rare deficient variant (possible null allele). Consistency of A1AT concentration with clinical symptoms and determined phenotype is considered sufficient for diagnostic purpose, although scientific proof of rare variant is still to be confirmed by A1AT gene sequencing.

Izvorni jezik
Engleski

Znanstvena područja
Kliničke medicinske znanosti, Farmacija

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