Abnormalities of Hepatic Protein Metabolism

This chapter will concentrate on alpha-1-antitrypsin deficiency, tyrosinemia, and urea-cycle enzyme defects. Alpha-1-antitrypsin deficiency is associated with liver and lung disease. Liver cirrhosis is a known complication. The Z variant is associated with liver and lung disease in smokers and results in the deposition of alpha-1-antitrypsin in the liver hepatocytes. The diagnosis of alpha-1-antitrypsin depends on phenotyping of the patient. A number of treatments have been described, however, the most effective therapy once the patient has developed liver cirrhosis is liver transplant.Tyrosinemia results from a deficiency in fumarylacetoacetate hydrolase enzyme. This enzyme deficiency leads to the accumulation of fumarylacetoacetate and their derivatives, succinylacetone, in various tissues. This results in hepatic dysfunction early in life. These patients usually present with vomiting, diarrhea, hepatosplenomegaly, edema, ascites, and bleeding diathesis. Some of these patients will have renal dysfunction, porphyria-like illness, or cardiomyopathy. Hepatocellular carcinoma is a known complication. The diagnosis depends on the presence of succinylacetone in the urine. The treatment is to utilize Nitisinone. However, the mainstay treatment for patients who develop end-stage liver disease is liver transplantation.Defects in urea-cycle enzymes is associated with elevated ammonia levels resulting in a disease state. Clinically patients present early in life intolerance to proteins, vomiting, seizure disorders, lethargy, and progression to coma. Hyperammonemia is the characteristic feature of urea-cycle enzyme defect. There are five enzymes involved in the formation of urea and any defects in these enzymes result in urea-cycle enzyme defects. The treatment for this depends on adequate hydration and removal of ammonia. A number of nitrogen-scavenging medications, such as sodium phenylacetate, act by providing an alternative route for excreting nitrogen precursors.