Overview Snapshot A 2-month-old boy is brought to the pediatrician by his parents due to feeding difficulties and an “enlarged” abdomen. On physical exam, there is insufficient weight gain and hepatosplenomegaly. On laboratory testing, there is a decrease in high-density lipoprotein (HDL)- cholesterol, elevated triglycerides, and an increase in LDL-cholesterol. Residual acid sphingomyelinase activity in peripheral blood leukocytes is <10% of controls. Introduction Clinical definition a lipid storage disorder due to sphingomyelinase deficiency ETIOLOGY Pathophysiology pathobiology sphingomyelinase deficiency results in the accumulation of sphingomyelin (a type of ceramide phospholipid), which deposits in the central nervous system (NPD type A) liver and spleen (NPD type A and B) lung and bone marrow (NPD type B) Genetics inheritance pattern autosomal recessive mutations chromosome 11p gene SMPD1 gene protein encoded for sphingomyelinase Associated conditions medical conditions and comorbidities hepatosplenomegaly (NPD type A and B) neurodegenerative disease (NPD type A) Epidemiology Incidence rare, however in Niemann-Pick disease (NPD) type A, it is more common in the Ashkenazi Jewish population Demographics 1:1 male-to-female ratio age bracket dependent on type of NPD type A can present as early as 3 months of age type B typically occurs in early childhood Location neural tissue (NPD type A) and visceral organs such as the spleen and liver (NPD type A and B); as well as the lung and bone marrow (NPD type B) Presentation Symptoms failure to thrive neurologic symptoms from demyelination Physical exam hepatosplenomegaly cherry red pot on macula STUDIES Labs residual acid sphingomyelinase activity is <10% of controls via peripheral blood leukocytes or cultured skin fibroblasts Histology lipid-laden macrophages ("foam cells") can be found in the liver, spleen, and bone marrow Treatment Conservative supportive care Complications Splenic rupture In patients with NPD type A, death is likely to occur by age 3 In patients with NPD type B, patients may survive into adulthood Prognosis Natural history of disease NPD type A is a fatal disease of infancy NPD type B has a more variable disease of presentation and age of onset; however, patients typically present in early childhood