Provided herein are methods and compositions for treating a subject suffering from an enzyme deficiency in the central nervous system (CNS). The bifunctional fusion antibody provided herein comprise an antibody to an endogenous blood brain barrier (BBB) receptor and an enzyme deficient in Tay Sachs disease (TSD), Nieman Pick Disease (NPD), or Neuronal Ceroid Lipofuscinosis 1 (NCL1), which are caused by mutations in the respective lysosomal enzymes, hexosaminidase A (HEXA), acid sphingomyelinase (ASM), and palmitoyl-protein thioesterase 1 (PPT1). The fusion antibodies provided herein comprise HEXA, ASM, and PPT1. The methods of treating an enzyme deficiency in the CNS comprise systemic administration of a fusion antibody provided herein.