Inherited metabolic disorders (IMD) of the liver are a heterogeneous group of rare diseases caused by a single defective enzyme in a metabolic pathway of hepatocytes. This often leads to the accumulation of toxic metabolites and the highly specific destruction of liver cells. For some IMD, simply replacing or correcting the deficient enzyme in a subset of hepatocytes is not sufficient to provide a cure due to the cell-autonomous pathophysiology of the disease.
Major advancements in the treatment of IMD are currently hampered by two important paradigms (see schematic).
