Alpha 1 antitrypsin deficiency in infants with neonatal cholestasis
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Updated: Apr 30, 2026
Isolation of Neonatal Extrahepatic Cholangiocytes
Published on: June 5, 2014
Maryam Monajemzadeh1, Reza Shahsiah2, Mohammad Vasei2
1Department of Pathology, Tehran University of Medical Sciences, Tehran, Iran ; Infectious Disease Research Center, Children's Medical Center Hospital, Tehran University of Medical Sciences, Tehran, Iran.
Insights
Alpha1-antitrypsin deficiency (A1ATD) is rarely a cause of neonatal cholestatic liver disease in Iranian children. Genetic analysis found only 2.2% of infants carried a single S allele, suggesting A1ATD is not a major factor in this population.
Area of Science:
- Hepatology
- Genetics
- Pediatrics
Background:
- Alpha1-antitrypsin deficiency (A1ATD) is a significant cause of pediatric liver transplantation.
- Gene frequencies of A1ATD alleles (Z and S) differ across ethnic groups.
Purpose of the Study:
- To determine the frequencies of the Z and S alleles of alpha1-antitrypsin deficiency (A1ATD) in Iranian infants with idiopathic neonatal cholestasis.
- To assess the role of A1ATD as an etiologic factor in this patient group.
Main Methods:
- A single-center study analyzed 87 liver biopsies from infants with cholestasis, excluding biliary atresia.
- DNA was extracted from formalin-fixed paraffin-embedded blocks.
- Alpha1-antitrypsin (AAT) genotype was determined using polymerase chain reaction (PCR) for S and Z alleles, followed by sequencing.
Main Results:
- The study included 87 infants (55.2% male) with a median age of 60 days.
- Two infants (2.2%) were heterozygous for the S allele.
- No individuals with ZZ, SS, or MZ genotypes were identified; no other polymorphisms were detected.
Conclusions:
- Alpha1-antitrypsin deficiency (A1ATD) appears to be an infrequent cause of neonatal cholestatic liver disease in Iran compared to other populations.
- Further research is recommended to accurately determine the prevalence of mutant AAT genes in Iran.
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.
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