A 35-year-old man is evaluated in the clinic for symptoms of shortness of breath. He reports no other lung or heart disease. He smokes half pack a day for the past 10 years. On examination, his JVP is at 2 cm, heart sounds normal, and lungs are clear. A CXR shows hyperinflation and increased lucency of the lung fields. A chest CT reveals bullae and emphysematous changes in the lower lobes, while pulmonary function tests show an FEV1/FVC ratio of < 70%. Evaluation of his family reveals other affected individuals. Which of the following is the most likely diagnosis?
Most people have two MM genes and a resultant alpha 1-antitrypsin level in excess of 2.5 g/L. Homozygotes with ZZ or SS genotypes have severe alpha 1-antitrypsin deficiency and develop severe panacinar emphysema in the third or fourth decade of life. Smoking is an important cofactor in the development of disease. Heterozygotes (MZ or MS) have intermediate levels of alpha 1-antitrypsin (i.e., genetic expression is that of an autosomal codominant allele). This heterozygous state is common (5-14% of general population), but it is unclear whether it is associated with lung function abnormalities.
alpha 1-antitrypsin deficiency
beta-glycosidase deficiency
glucose-6-phosphatase deficiency
glucocerebrosides deficiency
Respiratory