Alpha-1 antitrypsin phenotypes in patients with Klinefelter's syndrome

Klinefelter’s syndrome (KS) is the most common human sex chromosome disorder, with a prevalence of 1 in 660 men. The phenotype is variable, but the most constant findings are small and firm testes, decreased testosterone level, infertility, eunuchoid body proportion, increased height, and learning disabilities, due to the presence of extra X chromosome(s) (Smyth and Bremner 1998). KS patients have frequently other diseases of lung, skin, liver and kidney (Morales et al. 1992; Swerdlow et al. 2005). Restrictive lung defects have been attributed to chest wall abnormalities, decreased respiratory muscle strength and increased chest wall compliance (Huseby and Petersen 1981). The likely cause is, decrease of lung compliance due to diminished elasticity of the lung matrix, but its biochemical cause is unknown (Morales et al. 1992). One of the causes could be the mutations in the alpha-1 antitrypsin (AAT) gene (SERPINE1), which is highly polymorphic, with more than 100 alleles identified so far. The alleles are categorized into normal, deficient and null variants on the basis of the plasma level and function of AAT. The protein phenotype is classified according to the ‘Pi’ (protease inhibitor) system, as defined by plasma isoelectric focusing. Normal Pi M types account for 95% of alleles in Caucasian individuals and are characterized by normal plasma levels. Pi X is a rare normal allele variant. Pi Z, S and null types are the most frequent AAT deficiency variants described in lung pathology, but Pi ZZ is associated with both pulmonary and liver diseases (Kaczor et al. 2007; Greene et al. 2008). AAT gene is located on chromosome 14q32.1 (Schroeder et al. 1985).