This review will focus in particular on two autosomal recessive disorders, mucopolysaccharidosis type I (MPS-I) (OMIM # 607014), caused by a deficiency of the enzyme alpha-L-iduronidase, and metachromatic leukodystrophy (MLD, OMIM # 250100), due to deficiency of arylsulfatase A (ARSA) enzyme, as models of LSD with nervous system involvement, for which different gene therapy (GT) approaches have been developed in the last few years. The gene discussed is IDUA; the disease is metachromatic leukodystrophy.