title: Alpha-1-antitrypsin deficiency in children: liver disease is not reflected by low serum levels of alpha-1-antitrypsin - a study on 48 pediatric patients.
abstract: BACKGROUND
  Alpha-1-antitrypsin (alpha1-AT) is an important protease inhibitor. The phenotypes are characterized by a low total serum alpha1-AT or by an abnormal protein accumulating in the hepatocytes. The aim of our study was to examine a correlation of total serum alpha1-AT, phenotype, and liver involvement in pediatric patients.
  
  
  METHODS
  48 patients, deficient for alpha1-AT were included. The phenotypes for alpha1-AT were determined by isoelectric focusing. Liver disease was defined either as elevated transaminases or/and as elevated conjugated bilirubin and gammaGT. Patients were reexamined after a mean interval of 2 years.
  
  
  RESULTS
  Homozygous alpha1-AD was found in 12 patients, heterozygous in 24 patients. In 12 children rare variants of alpha1-AD were diagnosed. Serum alpha1-AT levels less than 60% of normal were found in all patients with homozygous, in 37% of patients with heterozygous alpha1-antitrypsin deficiency (alpha1-AD), and in patients with the homozygous variant PiM(palermo). Liver disease was found in 8/12 patients with the phenotype PiZZ and in 15/24 patients with heterozygous alpha1-AD. Three of 4 patients with the phenotype PiMQ0 had severe liver disease despite normal serum levels for alpha1-AT. In 11 patients with heterozygous alpha1-AD liver disease was apparent despite normal serum alpha1-AT levels. In two patients with the variant type Mpalermo serum levels were as low as 11% of normal without any signs of liver disease.
  
  
  CONCLUSIONS
  Our data clearly show that in the diagnostic workup of neonatal cholestasis measurement of total serum alpha1-AT does not exclude liver disease due to abnormal alpha1-AT variants. We suggest analysis of alpha1-AT-phenotype by isoelectric focussing in patients with unknown liver disease. Heterozygous or rare variant types might remain undiagnosed by measuring total alpha1-AT only.
authors.affiliation: Children's Hospital, Dr. v. Haunersches Kinderspital, University of Munich, Germany. thomas.lang@med.uni-muenchen.de
authors.forename: Thomas
authors.initials: T
authors.lastname: Lang
authors.forename: M
authors.initials: M
authors.lastname: Mühlbauer
authors.forename: M
authors.initials: M
authors.lastname: Strobelt
authors.forename: S
authors.initials: S
authors.lastname: Weidinger
authors.forename: H B
authors.initials: HB
authors.lastname: Hadorn
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D002779:Cholestasis / Q000097:blood / Q000209:etiology / Q000473:pathology; D005260:Female; D005838:Genotype; D006505:Hepatitis / Q000097:blood / Q000209:etiology / Q000473:pathology; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007525:Isoelectric Focusing; D008103:Liver Cirrhosis / Q000097:blood / Q000209:etiology / Q000473:pathology; D008107:Liver Diseases / Q000097:blood* / Q000209:etiology / Q000473:pathology; D008111:Liver Function Tests; D008297:Male; D010641:Phenotype; D012189:Retrospective Studies; D000515:alpha 1-Antitrypsin / Q000032:analysis* / Q000737:chemistry; D019896:alpha 1-Antitrypsin Deficiency / Q000097:blood* / Q000150:complications / Q000473:pathology
chemical_list: D000515:alpha 1-Antitrypsin