Progressive Hyperammonemia and Insulin Resistance After Portacaval Shunt in Homozygous Familial Hypercholesterolemia

Abstract

We have followed-up four homozygous hypercholesterolemia children who had undergone an end-to-side portacaval shunt. Periodic evaluations of protein and carbohydrate tolerance after surgery have been performed. The surgery was done at ages ranging between 5 to 12 years. They have been followed-up for up to nine years. Before surgery, their plasma cholesterol levels ranged between 437 mg/dL and 1300 mg/dL. These have been reduced to about 50% with a gradual regression of xanthomas. The plasma triglycerides have been restored to normal. Protein loading tests were performed regularly. After surgery, fasting and post-load ammonia levels are abnormally high, indicating protein intolerance which becomes progressively more severe with time. A clinical trial with benzoate has shown that the excretion of hippurate nitrogen increases at the expense of urinary urea nitrogen. In one of the patients, the fasting plasma ammonia became normal during benzoate therapy with a reduction in plasma glutamine nitrogen. A standard oral glucose tolerance test was conducted in each of these children before and after portacaval shunt. Whereas no differences are discernible between the glucose curves for the pre-shunt and post-shunt periods, there is a tendency for insulin to increase progressively after shunt with the highest values being recorded after 8 years in one patient. At the same time, an increase in plasma growth hormone level was noted.

In conclusion, patients with familial homozygous hypercholesterolemia treated with portacaval shunt develop progressive protein intolerance and secondary hyperammonemia. This may be caused by the diversion of ammonia-rich portal blood and a progressive decrease in the hepatic functional capacity. It is thus important that protein intake in these children be controlled. Eeriodic sodium benzoate therapy could help to eliminate the nitrogen overload. Hyperinsulinemia develops progressively after surgery indicating an insulin resistance. The increase in growth hormone after shunt may be one of the factors responsible for insulin resistance and it is probable that a carbohydrate intolerance may eventually develop.