Hyperammonemic Encephalopathy in Fast Growing Hepatic Tumors: a New Physiopathological Pathway Proved by Molecular Biology That Resulted in Adequate Treatment and Full Neurocognitive Recovery

Ammonia is a nitrogen compund miscible with water. When ammonia blood level increases, it enter the central nervous system in excessive quantities leading to astroglial cells swelling, astrocyte phenotipe transformation to Alzheimer's type II cells and increased oxidative stress, leading to severe neurological toxicity and encephalopathy. Fast growing hepatic tumors and fibrolamellar hepatocellular carcinoma hve been associated with hyperammonemic encephalopathy. Many physiopathological explanations were described and teatment options proposed, but they were all based in suppositions and did not reach a consensus. We performed gene testing and RNA expression analysis to demonstrate a new physiopathological pathway to hyperammonemia in patients with fast growing hepatic tumors that envolves c-Myc overexpression in the poliamine synthesis that results in ornithine decarboxylase and ornithine transcarboxylase dysfunctions that culminates in urea cycle disorder and hyperammonemia. This allows a different treatment option then previously reported and full neurological recovery. All patients with hepatic tumors that develop neurocognitive disorders should be tested for serum ammonia level. This may allow prompt and adequate treatment to a non-enherited urea cycle disorder and complete clinical recovery.