Niemann-Pick Diseases; largest Iranian cohort with genetic analysis

Background: Niemann-Pick diseases (NPD) is an autosomal recessive inherited lysosomal lipid storage disorder which occurs due to a defect in cellular cholesterol trafficking, leading to excess lipid accumulation in multiple organ systems such as the brain, lungs, spleen and liver. SPMD1-associated disease includes classic infantile and visceral NPD type A and B respectively. Type C NPD is subacute or juvenile. Methods: Sanger sequencing of the candidate genes for NPD were performed followed by bioinformatic analysis to confirm the types of NPD and to identify novel mutations. All patients underwent full clinical assessment. Results: In this case series, we present two cases with NPD type A, six cases with NPD type B, and 11 cases with type C with various enzymatic defects identified in these cases. Within these 19 patients we present seven previously reported mutations and 10 novel mutations causing NPD. Conclusion: Our report demonstrates that NPD has a variable age of onset and can present early in life. In this study, we investigated the clinical and genetic manifestations of a large Iranian cohort. Understanding the variable presentation of NPD will allow for clinicians to have a high index of suspicion for the disease.