A rare case of alpha 1-antitrypsin deficiency associated with hypogammaglobulinemia and recurrent pulmonary thrombosis
A 89-year-old, non-smoking, Caucasian woman with past medical history of AATD, recurrent pneumonias, dementia, diabetes mellitus and hypertension presents with productive cough and exertional dyspnea. During the seventh decade of her life, she was diagnosed with bronchiectasis and showed persistent decline of her health. She incurred recurrent pneumonias due to pseudomonas, empyema thoracis and mycobacterial infections and further laboratory investigation revealed AAT serum level of 24 mg/ml (83-199 mg/dl) with ZZ phenotype.\nOn admission, physical exam revealed she was febrile and had bilateral crepitations at the lung bases. Laboratory diagnostics revealed white cell count of 13.6 × 109/l with a differential of 80% neutrophils, 11% bands, 5% lymphocytes, 2% monocytes and 2% eosinophils. Liver function test include alanine transaminase of 27 U/l, aspartate transaminase of 28 U/l, alkaline phosphatase of 130 U/l, total bilirubin of 0.1 mg/dl, albumin of 3.1 g/dl and total protein of 5.6 g/dl. A chest radiography showed bilateral infiltrates followed with a chest computed tomography which revealed bilateral lower lobe segmental pulmonary arterial filing defects consistent with pulmonary emboli and marked emphysema with lower lobe cystic bronchiectasis and nodular infiltrates []. The patient was initiated on heparin and warfarin anticoagulation therapy along with the intravenous antibiotics of vancomycin 1 g every 12 h and cefepime 1 g every 12 h. Sputum cultures grew pseudomonas but acid fast bacilli, viral, fungal and blood cultures remained negative. An echocardiogram did not show evidence of endocarditis. Subsequently, patient showed remarked clinical and physiological improvement and antibiotic vancomycin was discontinued. Pulmonary function tests demonstrated severe obstructive lung disease with forced expiratory volume in 1 second (FEV1) of 37%, FEV1/forced vital capacity of 61% and total lung capacity of 121%. Given the recurrent infections, immunoglobulin levels were checked and were suggestive of gamma immunoglobulin (IgG) of 514 mg/dl (normal 694-1618 mg/dl), immunoglobulin M of 30 mg/dl (normal 48-271 mg/dl) with normal immunoglobulin A of 270 mg/dl (normal 81-463 mg/dl). Antibody levels specific for capsular polysaccharides of Streptococcus pneumoniae and for tetanus toxoid were found low. She received monthly intravenous immunoglobulin infusions for immunoglobulin deficiency. Patient got discharged to home with oral anticoagulant warfarin and intravenous cefepime for completion of total 14 days. During follow-up of the patient, her episodes of recurrent infections decreased relatively, however she continued to have pulmonary emboli. Her coagulation profile revealed protein C of 29 μ/dl (normal 75-165 μ/dl), anti-thrombin III of 85 μ/dl (normal 85-130 μ/dl) with negative factor V mutation, lupus anticoagulant and cardiolipin antibody.