Secondary Ammonia Scavenge With Glycerol Phenylbutyrate Improves Hyperammonemia Following Portosystemic Shunting.

Portosystemic shunts are used to treat portal hypertension arising from extrahepatic portal venous obstruction. They decompress the portal system by allowing intestinal blood to bypass the liver and enter directly into the systemic circulation. These shunts increase the risk of minimal hepatic encephalopathy and altered neurodevelopmental outcomes in affected children. Treatment options are limited and have been extrapolated from those used in cirrhosis. We describe the use of glycerol phenylbutyrate as an alternate management strategy. A 3-year-old boy underwent distal splenorenal shunt for refractory variceal bleeding secondary to portal hypertension. He had neurologic deterioration and hyperammonemia refractory to traditional management strategies. Glycerol phenylbutyrate was initiated and resulted in a sustained improvement in ammonia levels, behavior, and school performance. This case illustrates the successful use of glycerol phenylbutyrate in a noncirrhotic patient with Portosystemic shunt and minimal hepatic encephalopathy refractory to conventional management strategies.

Two Siblings With Valproate-Related Hyperammonemia and Novel Mutations in Glutamine Synthetase (GLUL) Treated With Carglumic Acid.

This case report describes 2 siblings with myoclonic epilepsy who had novel mutations in the glutamine synthetase (GLUL) gene: c.316C>T, p.(Arg106*) and c.42G>C, p.(Lys14Asn). Valproic acid improved seizure control, but was associated with hyperammonemic encephalopathy. Addition of carglumic acid reduced ammonia levels but drug coverage was declined. We therefore designed a protocol to measure the reduction in plasma ammonia in response to carglumic acid therapy. After the first dose of carglumic acid, Patient 1 showed a reduction in plasma ammonia levels within 3 hours, from 114 umol/L to 68 umol/L (reference 12-47 umol/L), and Patient 2 from 108 umol/L to 80 umol/L, which was sustained over a 2 week period. Overall, there was a strong negative correlation between plasma ammonia levels and carglumic acid levels (r = -0.86, p = 0.0013), and recurrence of hyperammonemic encephalopathy was not observed while the patients were taking carglumic acid.