Alpha 1 antitrypsin deficiency in children with chronic liver disease in North India

Abstract

We attempted to determine the role of alpha-1-antitrypsin (AAT) deficient variants as an etiologic factor for chronic liver disease in North Indian children. This study investigated 1700 children (682 retrospectively and 1018 prospectively) (840 CLD, 410 neonatal cholestasis and 450 without liver disease) for AAT deficiency. Tertiary referral center, All India Institute of Medical Sciences, New Delhi. Of 1250 liver disease patients, 98 (7.8%) were suspected to be AAT deficient on the basis of screening tests (low serum AAT levels and/or absent/faint alpha-1-globulin band on serum agarose electrophoresis and/or diastase resistant PAS positive granules on liver biopsy). AAT deficient Z or S allele in suspected patients. Z or S allele was not observed on phenotyping (1700 subjects), or with PCR-RFLP, SSCP and sequencing done in 50 of 98 suspected AAT deficient patients. A novel mutation G-to-A at position 333 in exon V was found in two siblings having positive immunohistochemistry for AAT on liver biopsy, both of whom had significant liver disease with portal hypertension. In conclusion, AAT deficiency as an etiologic factor for chronic liver disease in childhood appeared to be uncommon in North India.