Studies have shown that hyperammonemia and peripheral inflammation play synergistic roles in inducing cognitive and motor alterations in HE.[45] The emergence of neurological alterations is mediated by the induction of neuroinflammation, which alters glutamatergic and GABAergic neurotransmission, leading to cognitive and motor disorders.[46,47] TNF, as a critical cytokine, can induce a wide range of intracellular signal pathways including apoptosis and cell survival as well as inflammation and immunity. This evidence concerns the gene TNF and hereditary elliptocytosis.