title: Diagnosis of alpha-1-antitrypsin deficiency by DNA analysis of children with liver disease.
abstract: BACKGROUND
  Alpha-1-antitrypsin deficiency is a genetic disorder which is transmitted in a co-dominant, autosomal form. Alpha-1-antitrypsin deficiency affects mainly the lungs and the liver leading, in the latter case, to neonatal cholestasis, chronic hepatitis or cirrhosis. A precise diagnosis of Alpha-1-antitrypsin deficiency may be obtained by biochemical or molecular analysis.
  
  
  OBJECTIVE
  The purpose of this study was to use DNA analysis to examine the presence of an alpha-1-antitrypsin deficiency in 12 children suspected of having this deficiency and who showed laboratory and clinical characteristics of the disease.
  
  
  METHODS
  Twelve patients, aged 3 months to 19 years, who had serum alpha-1-antitrypsin levels lower than normal and/or had hepatic disease of undefined etiology were studied. The mutant alleles S and Z of the alpha-1-antitrypsin gene were investigated in the 12 children. Alpha-1-antitrypsin gene organization was analyzed by amplification of genome through the polymerase chain reaction and digestion with the restriction enzymes Xmnl (S allele) and Taq-1 (Z allele).
  
  
  RESULTS
  Seven of the 12 patients had chronic liver disease of undefined etiology and the other five patients had low serum levels of alpha-1-antitrypsin as well as a diagnosis of neonatal cholestasis and/or chronic liver disease of undefined etiology. Five of the 12 patients were homozygous for the Z allele (ZZ) and two had the S allele with another allele (*S) different from Z.
  
  
  CONCLUSIONS
  These results show that alpha-1-antitrypsin deficiency is relatively frequent in children with chronic hepatic disease of undefined etiology and/or low alpha-1-antitrypsin levels (41.6%). A correct diagnosis is important for effective clinical follow-up and for genetic counseling.
authors.affiliation: Departments of Pediatrics, Medical Genetics, Anatomical Pathology and Clinical Pathology, Faculty of Medical Sciences (FCM), State University of Campinas-UNICAMP, Caixa Postal 6111-13083-970-Campinas, SP, Brazil. amdetommaso@hotmail.com
authors.forename: A M
authors.initials: AM
authors.lastname: De Tommaso
authors.forename: C L
authors.initials: CL
authors.lastname: Rossi
authors.forename: C A
authors.initials: CA
authors.lastname: Escanhoela
authors.forename: H G
authors.initials: HG
authors.lastname: Serra
authors.forename: C S
authors.initials: CS
authors.lastname: Bertuzzo
authors.forename: G
authors.initials: G
authors.lastname: Hessel
mesh_terms: D000293:Adolescent; D000328:Adult; D000483:Alleles; D001706:Biopsy; D002648:Child; D002675:Child, Preschool; D004247:DNA / Q000032:analysis*; D005784:Gene Amplification; D005838:Genotype; D006801:Humans; D007223:Infant; D008107:Liver Diseases / Q000209:etiology* / Q000473:pathology; D009154:Mutation; D016133:Polymerase Chain Reaction; D015183:Restriction Mapping; D000515:alpha 1-Antitrypsin / Q000032:analysis / Q000235:genetics; D019896:alpha 1-Antitrypsin Deficiency / Q000175:diagnosis* / Q000235:genetics
chemical_list: D000515:alpha 1-Antitrypsin; D004247:DNA