Acid sphingomyelinase deficiency (ASMD) – also known as Niemann-Pick (NP) disease – is a rare, autosomal recessive disorder which is characterized by deficiency of the lysosomal enzyme acid sphingomyelinase (ASM), thus resulting in excessive storage of lipids in organs (i.e. spleen, liver, lung, bone marrow, lymph nodes, and vascular system). Literature provided few cases of moderate-to-severe valvular heart disease due to ASMD, mostly in adulthood. We reported the case of a patient with B-subtype NP disease which was diagnosed during his adulthood. NP disease was associated to situs inversus. Specifically, a severe, symptomatic aortic stenosis was also identified and the need for surgical or percutaneous intervention was deemed. The heart team chose Trans Aortic Valvular Implantation (TAVI) which was successfully performed with no further complications at follow-up.