Liver disease in alpha1-antitrypsin deficiency detected by screening of 200,000 infants

N Engl J Med. 1976 Jun 10;294(24):1316-21. doi: 10.1056/NEJM197606102942404.


We prosepctively studied 200,000 newborns to determine the frequency and clinical characteristics of alpha1-antitrypsin deficiency. One hundred and twenty Pi Z, 48 Pi SZ, two PI Z-and one Pi S-infants were identified and followed to the age of six months. Fourteen of 120 Pi Z infants had prolonged obstructive jaundice, nine with severe clinical and laboratory evidence of liver disease. Five had only laboratory evidence of liver disease. Eight other Pi Z infants had minimal abnormalities in serum bilirubin and hepatic enzyme activity and variable hepatosplenomegaly. All 22 Pi Z infants with hepatic abnormalities, two thirds of whom were made, appeared healthy at six months of age. Ninety-eight Pi Z infants did not have clinical liver disease, but liver-function tests gave abnormal results in 44 of 84 at three months, and in 36 of 60 at six months of age. The number of small-for-gestational-age infants was greater (P less than 0.001) among those with clinical liver disease. None of the 48 Pi SZ infants had clinical liver disease, but 10 of 42 at three months and one of 22 at six months of age had abnormal liver function. The Pi Z and Pi SZ phenotypes are associated with covert or readily apparent hepatic dysfunction in the first three months of life.

MeSH terms

  • Alleles
  • Cholestasis / enzymology
  • Cholestasis / genetics
  • Chronic Disease
  • Female
  • Follow-Up Studies
  • Genotype
  • Humans
  • Infant
  • Infant, Newborn
  • Infant, Newborn, Diseases / enzymology*
  • Infant, Newborn, Diseases / genetics
  • Liver / enzymology
  • Liver Cirrhosis / enzymology
  • Liver Cirrhosis / genetics
  • Liver Diseases / enzymology*
  • Liver Diseases / genetics
  • Male
  • Phenotype
  • Sex Factors
  • alpha 1-Antitrypsin Deficiency*