Contributor: Gordon K. Klintworth
Niemann-Pick disease (sphingomyelin lipidosis, sphingomyelin storage disease, the Niemann-Pick group of diseases, sphingomyelin-cholesterol lipidoses, OMIM #257200) includes a group of inherited disorders with an intracytoplasmic storage of sphingomyelin that vary in phenotype and in the activity of sphingomyelinase. Almost all forms of this lysosomal storage disease has characteristic foam cells in the spleen, bone marrow, lungs, and lymph nodes. These lipidoses are a heterogenous group of disorders of lipid metabolism [lipid metabolism - disorder] characterized by hepatosplenomegaly and an accumulation of sphingomyelin, gangliosides, and cholesterol in the brain and other viscera. The lipid storage is present within lysosomes of ganglion cells, macrophages, and other cells. The appearance of the stored material in routine hematoxylin and eosin stained tissue sections has been likened to an opening rose. "Sea-blue" histiocytes (which as also found in other diseases) may also be present. Ocular abnormalities occur in almost all types of Niemann-Pick disease, but many of the early published ocular manifestations of this lipidosis can not be correlated with currently recognized types. Several classifications of Niemann-Pick disease have been proposed over the years. The Crocker classification of Niemann-Pick disease recognizes 5 types: Niemann-Pick disease type A, Niemann-Pick disease type B, Niemann-Pick disease type C, Niemann-Pick disease type D, Niemann-Pick disease type E. A more recent current classification divides Niemann-Pick disease into two types based on whether the sphingomyelin storage results from a primary deficiency of sphingomyelinase (Niemann-Pick disease type I) or whether the sphingomyelin storage is secondary to an uncertain primary defect (Niemann-Pick disease type II). The differential diagnosis of Niemann-Pick disease includes Gaucher disease. Numerous multilamellar intracytoplasmic inclusions (ranging in diameter from 0.2 to 3.0 µm and with lamellae having periodicities of 5.5 to 6.5 nm) and surrounded by single membranes are evident in various ocular tissues (including ganglion cell layer of the retina, amacrine cells, retinal pigment epithelium, Müller cells, keratocytes, corneal endothelium, and corneal epithelium, and the lens epithelium) by transmission electron microscopy. Another type of inclusion body has dense lamellar structures that alternate with granular, vacuolar, or whorled masses, is abundant in many ocular cells (including Müller cells, conjunctival epithelium, corneal epithelium, keratocytes, ciliary muscle, choroidal fibroblasts). This inclusion is birefringent under polarized light and probably represents a specific structure of the lamellae (a "head-and-tail" orientation of the polar (phosphocholine) and nonpolar (ceramide) moieties of sphingomyelin).Conjunctival abnormalities from the storage of sphingomyelin and/or cholesterol appear to be unique to Niemann-Pick disease.