1- Antitrypsin Deficiency

CASE REPORT The patient was a 35-year-old white male with 1-antitrypsin deficiency. He received a combined liver-kidney transplant for cirrhosis complicated by portal hypertension, renal insufficiency secondary to

and hard.The spleen was palpable 6 cm below the left costal margin. No other physical abnormalities were noted. The child's laboratory tests revealed a normal hematological picture except for a platelet count of 122,000/mm3 (below normal). He had normal liver enzymes except for a serum glutamic oxaloacetic transaminase level of 197 units/mL (mildly increased). Both his blood urea nitrogen (BUN) and creatinine levels were normal. The patient's serum protein electrophoresis was abnormal, with a low serum albumin of 2.9 g/dL (normal 3.3-4.6 g/dL) and an 1-globulin band that was barely visible. Because of this last finding, protease inhibitor (PI) phenotyping was done on the child and his family. The child's phenotype was PIZZ, while both parents had the heterozygote, that is, the PIMZ phenotype. The nomenclature of the PI types is based on the elcctrophoretic mobility of the various PI types at pH 4.9. PiMM represents the homozygous normal allele; letters alphabetically before M designate anodal

membranoproliferative glomerulonephritis, and combined restrictive and obstructive pulmonary disease at age 18 years. Jaundice and pruritus were observed at age 6 weeks and resolved spontaneously after approximately 2 months. He was hospitalized for pneumonia at age 20 months, and an enlarged liver was noted. A percutaneous needle biopsy specimen from the liver was interpreted to show postnecrotic cirrhosis, although reevaluation of the biopsy specimen showed the presence of globules that were periodic acid-Schiff (PAS) positive, diastase resistant. He was then referred to our institution at age 2.5 years for liver transplantation. At the time of the initial evaluation, the physical examination revealed a well-

developed young boy in no acute distress. He was not jaundiced; however, it was notable that he had a protuberant abdomen with a liver edge palpable 3 em below the right costal margin in the midclavicular line. The liver was nontender

variants, and those after M designate cathodal variants. The child's subsequent course was one of gradual hepatic deterioration. At age 3 years, he was noted to have ascites (intra-abdominal

fluid accumulation). This progressed slowly until the age of 6 years, when severe ascites and peripheral edema necessitated the initiation of spironolactone (a potassium-sparing

obstruction and destruction of alveolar lung tissue, consistent with emphysema. No further pulmonary problems occurred until the patient was age 16 years, when he developed occasional episodes of bronchospasm (spasmodic contraction of the smooth muscles of the bronchus). Pulmonary function studies at that time, though improved from those immediately following his pneumothorax, still revealed combined obstructive and destructive lung disease. Also at about age 12 years, the patient began to experience episodes of acute hepatic encephalopathy (graded onset of coma brought on by circulating false neurotransmitters). The first of these episodes was the most severe. The patient entered the hospital in a confused and disoriented state and with an elevated ammonia level. The immediate problem was easily controlled with neomycin (a nonabsorbable antibiotic that kills intestinal, ammonia-forming bacteria) enemas. During this admission, gastrointestinal bleeding developed, exacerbating the hyperammonemia (plasma ammonia of 450 mol/L; normal < 35 mol/L). The patient gradually slipped into grade IV hepatic coma with fundoscopic changes consistent with increased intracranial pressure. Coagulopathy (increased bleeding tendency) prevented placement of an intracranial pressure monitor. He was treated empirically for presumed cerebral edema associated with acute hepatic encephalopathy with

diuretic). Several admissions to the hospital were required over the next 6 years for ascites with scrotal edema. Serum albumin values were persistently low, less than 2.0 g/dL. During this time, the patient also had two episodes of primary peritonitis (intraperitoneal infection) and one episode of a-streptococcal sepsis. By age 11 years his renal function decreased, as measured by a creatinine clearance of 71 mL/min (normal is 105 mL/min). He also developed protein-losing nephropathy with a 24-hour urinary protein excretion of 600 mg that increased to 14 g after albumin infusions (normal urinary protein excretion is 100 mg/24 h). Because of abnormal coagulation studies, renal biopsy was deferred; however, the clinical picture was consistent with the membranoproliferative glomerulonephritis seen in 1- antitiypsin deficiency. At age 12, the patient was admitted with acute chest pain from a left spontaneous pneumothorax (air within the pleural cavity).This required hospitalization and chest tube insertion, but he recovered without sequelae. After the resolution of this problem, pulmonary function testing revealed findings of both severe airway

hyperventilation, a mannitol drip, and barbiturate coma. The patient recovered without neurological sequelae. Despite protein restriction (1.0 g protein per kilogram body weight per day), the patient had two other milder episodes of hyperammonemia over that year. He continued on limited protein intake, neomycin, and lactulose, with periodic monitoring for subclinical hepatic encephalopathy by electroencephalography. Despite these complications of 1-antitrypsin deficiency, he maintained an active life, attending school and camping with his parents. By the age of 16 years, his renal condition had deteriorated considerably, with a creatinine clearance of only 23 mL/min. He was therefore accepted as a candidate for a combined liverkidney transplant. After a 2-year wait for an immunologically compatible donor, the

transplant was successfully performed at age 18 years at the University of Minnesota Hospitals. He completed high school and was employed full time in good health for over a decade. Seventeen years after his transplant, he was found to have cirrhosis from hepatitis C, likely acquired from the many blood transfusions he required prior to and during his transplantation. He died awaiting a second hepatic transplant.