Liver-directed therapy by systemic administration of LVs to treat disease states caused by monogenic mutations, such as ADA-deficiency, mucopolysaccharidoses (MPS: I, IIIa, VII), or hemophilia (Factor VIII or IX) may require re-administration of vector at some point after the initial treatment, because there is currently no evidence that cells with self-renewing capacity are transduced. This evidence concerns the gene COX8A and hyperinsulinemic hypoglycemia, familial, 4.