Introduction: Niemann-Pick type C (NPC) is an autossomal recessive disorder of cholesterol intracellular trafficking. The age of presentation extend into adulthood and the late forms have dominant neurological and psychiatric affectations. Substract deprivation therapy with miglustat could changed the course of the disease Case Reports: We present two brothers with the diagnosis of NPC at 21 and 26 years old. The first patient presented at 21 years old. He had an excellent school performance until 19 years old, when he begun a slow neurological deterioration associated with dysartic speech, saccadic eye movements, limb hypotonia, dismetry and an ataxic broad based gait. The biochemical study of cholesterol intracellular trafficking in fibroblasts confirmed NPC.The mollecular study identified a mutation in NPC1 gene. His oldest brother was being followed in Psychiatric consultation for psycosis and the same NPC1 gene mutation was confirmed. Both started therapy with miglustat. Four years later, the neurological picture is stabilized with a significative improvement in brain metabolic pattern in positron emission tomography study (PET). Discussion: NPC late presentations present a diagnostic chalange for the physician. Substract deprivation therapy with miglustat determined a favorable evolution. PET scan give good information to monitor neurologic progression and treatment response. Backgroud: Pompe disease is an autosomal recessive lysosomal storage disorder caused by a deficiency of acid α-glucosidase. Accumulation of autophagosomes is a key factor for poor response to Enzyme replacement therapy in Pompe disease. We and others previously found that autophagy is also activated in patient fibroblasts. However, induction mechanism of autophagy in patient fibroblasts is not fully elucidated. In this study, we analyzed the glucose metabolism-related signaling pathway in patient fibroblasts to clarify their involvement in regulation of autophagy. Methods: Skin fibroblasts derived from infantile-onset patients with Pompe disease and normal infant were cultivated in the presence or absence of insulin, and were lysed with 2% SDS. These samples were analyzed by Western blotting using the antibodies against akt, and LC3. Results: The levels of phosphorylated akt were about 30-fold lower in patient fibroblasts than in normal fibroblasts, whereas the levels of LC3-II were about 7-fold higher in patient fibroblasts than in normal fibroblasts. When patient fibroblasts were treated with insulin, increased levels of phosphorylated akt and decreased levels of LC3-II were observed in them. Conclusion: These results suggest that activation of autophagy in fibroblasts from infantile-onset patients with Pompe disease is caused by downregulation of akt signaling. Conflict of Interest declared.