Since citrin is a crucial component of the MAS, citrin deficiency is also characterized by impaired MAS activity, disrupting the cytosolic and mitochondrial NAD+ and NADH levels and affecting multiple NAD+/NADH dependent metabolic pathways, including glycolysis, GNEO, TCA cycle and FFA β-oxidation (Figure 2C), all pathways that we found to be significantly affected in TNF-induced SIRS (Figure 1) (43). This evidence concerns the gene TNF and hyperinsulinemic hypoglycemia, familial, 4.