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Alpha-1 antitrypsin deficiency
  1. R A PRIMHAK,
  2. M S TANNER
  1. Institute of Child Health, University of Sheffield, Sheffield Children's Hospital, Western Bank, Sheffield S10 2TH, UK
  1. Dr Primhak email:r.a.primhak{at}sheffield.ac.uk Accepted 8 March 2001

https://doi.org/10.1136/adc.85.1.2

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    α-1 antitrypsin is synthesised in the liver and protects lung alveolar tissues from destruction by neutrophil elastase.1α-1 antitrypsin deficiency is a common autosomal recessive condition (1:1600 to 1:1800) in which liver disease results from retention of abnormal polymerised α-1 antitrypsin in the endoplasmic reticulum of hepatocytes, and emphysema results from alveolar wall damage. The clinical consequences of α-1 antitrypsin deficiency in childhood are haemorrhagic disease in infancy, cholestasis in infancy, or chronic liver disease. Lung disease attributable to α-1 antitrypsin deficiency does not occur in childhood, but is closely linked to smoking in adults. Membranoproliferative glomerulonephritis, panniculitis, and necrotising vasculitis are associations with α-1 antitrypsin deficiency in adult life.2-4 Diagnostic methods are summarised in table 1.

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    Table 1

    Diagnostic methods for identification of α-1 antitrypsin deficiency

    Phenotypes

    α-1 antitrypsin is a protease inhibitor, and commonPi variants have been named by their electrophoretic mobility. PiM, of which there are several minor variants, is the normal protein. PiZ, the mutant responsible for more than 95% of cases of pulmonary and hepatic disease associated with α-1 antititrypsin deficiency, is most frequent in Scandinavia and progressively less common as one travels south in Europe. PiS, by contrast, is most common in the Iberian peninsula.5

    Emphysema is associated both with null mutations (no protein produced) and with mutations producing defective or non-exported protein. Liver disease is associated only with those mutations that produce a peptide which forms loop sheet polymers that are retained in the liver, namely homozygotes for PiZ, PiM (Malton), and the compound heterozygotes PiZ−, PiSZ, and PiZI.6 The nomenclature of genetic variants is slightly confusing: presumed homozygous abnormalities such as PiZZ are conventionally referred to as PiZ unless the null gene has been excluded from the phenotype; thus PiZ might actually be PiZ− (Z plus null), or PiZZ. …

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