Alpha₁-antitrypsin deficiency with cirrhosis associated with the protease inhibitor phenotype SZ

Following the incidental finding of hepatomegaly in a 39 year old white man from the Dominican Republic, a liver biopsy disclosed chronic active hepatitis and cirrhosis. Six years later, after presenting with upper abdominal pains due to a duodenal ulcer, he was found to have a partial deficiency of alpha₁ antitrypsin associated with the rare protease inhibitor phenotype SZ. The serum alpha₁-antitrypsin concentration was 104 mg/100 ml and the serum tryptic inhibitory capacity 58 per cent of normal. Periodic acid-Schiff-positive diastase-resistant globules and abundant lipofuscin pigment were demonstrated in his hepatocytes. Despite the absence of appreciable cholestasis, copper was readily demonstrated in hepatocytes histologically, and the hepatic concentration of copper was very high (593 μg/g dry weight). A severe defect in pulmonary diffusion capacity (less than 40 per cent of the norm) was associated with an arteriovenous shunt index of 7 per cent, moderate arterial hypoxemia (oxygen tension (pO₂) 61 mm Hg), normal lung volumes and no roentgenologic or spirometric evidence of obstructive airway disease. Although the activities of trypsin and chymotrypsin in a fasting duodenal aspirate were normal, values for sweat sodium (90 meq/liter) and chloride (76 meq/liter) were high. Subsequently a polyarthritis developed without roentgenologic evidence of joint destruction. The patient died of liver cell failure. Additional findings noted at autopsy included hepatocellular carcinoma, mild emphysema affecting predominantly both lung apices and chronic fibrosing interstitial pneumonitis. The protease inhibitor phenotypes of 12 members of the patient's family were determined. A brother, who also had phenotype SZ, had no clinical or serum biochemical evidence of liver disease. Another brother, who had phenotype MS, had cirrhosis, probably secondary to alcoholism. It is suggested that patients with chronic liver disease associated with alpha₁antitrypsin deficiency be screened for evidence of abnormal copper retention and that treatment with d-penicillamine be considered in those with documented hepatic copper overload.