Alpha 1 Antitrypsin Deficiency in Infants with Neonatal Cholestasis|
Monajemzadeh, Maryam; Shahsiah, Reza; Vasei, Mohammad; Tanzifi, Parin; Rezaei, Nima; Najafi, Mehri; Soleimanifar, Narjes & Eghbali, Maryam
Objective: Alpha1-antitrypsin deficiency (A1ATD) is the most important indication for liver transplantation in
children. The gene frequencies vary in different ethnic groups. In the present study, we attempt to determine
the frequencies of the most common defective alleles, Z and S, in Iranian children suffering from idiopathic
neonatal cholestasis. Eighty-seven infants were typed for Z and S alleles.
Methods: In a single center study, 87 consecutive liver biopsies from infants with cholestasis were reviewed
and patients with neonatal cholestasis enrolled in the study and cases with confirmed biliary tract atresia
excluded. Formalin fixed paraffin embedded blocks were used for DNA extraction. AAT genotype was
determined by polymerase chain reaction (PCR) assay and amplification of the two most common deficiency
variants, S and Z alleles, and then sequencing of PCR products.
Findings: There were 48 (55.2%) males and 39 (44.8%) females, with a median age of 60 days. Out of 87 of
the study subject, 2 (2.2%) were heterozygous for the S allele, and no ZZ, SS or MZ individual was found in the
patients. No other polymorphism was found in the sequencing results.
Conclusion: In comparison to other populations, AAT deficiency seems not to be an important etiologic factor
for neonatal cholestatic liver disease in Iran; however, further studies are recommended to estimate the true
mutant gene frequencies.
Alpha1-antitrypsin Deficiency; Liver; Biopsy; Cholestasis; PCR; DNA Sequencing; Iran