Biochemistry: Group I patients have profound deficiency of lysosomal sphinomyelinase activity. Enzymological defects of group II is not clear.

Type A: Neonatal onset with hepatosplenomegaly and failure to thrive, mental retardation, and dementia in the later course of disease. Death usually occurs before 4 years of age. Prolonged survival is possible and patients develop spasticity, psychomotor retardation and seizures. Ocular examination will show cherry red spots at the macula.
Type B: This is the chronic non-neuropathic visceral form.
Type C: Patients have very variable clinical presentation.

Pathology of Nieman-Pick disease group I:

Storage: Increase of spingomyelin in both grey and white matter of the brain in type A. Brain spingomyelin level is normal in type B.

Histology:

CNS There many ballooned neurons and glia similar to Tay-Sachs disase. There is also marked demyelination with gliosis and numerous storage cells in the white matter.
Other organs: Marked hepatosplenomegaly. Type A and C may have vacuolated lymphocytes.
Niemann-Pick cells: They are foamy storage cells present throughout the mononuclear phagocyte system and are large (20-90 mm in diameter) and has a “mulberry-like”appearance with the cytoplasm filled with relatively uniform vacuoles. These cells are widely found in spleen, liver, bone marrow, and thymus. The lipid deposition is best detected in frozen sections. The storage material are positive for sudan black and ferric-hematoxylin; they also show red birefringence under polarized light.
Sea-blue histiocytes: They can be seen in type B disease. The cytoplasm of these cells is filled with small granule staining intensely blue with Giemsa or Wright stain.
EM: Neuronal inclusions are loosely packed lipid lamellae within membrane-bound vacuoles about 1-2 mm.

Pathology of Nieman disease group II: Although clinical features in this group are diverse, their pathology is almost identical.

Histology:

CNS and PNS: Neuronal ballooning can be seen in all regions and is particularly prominent in the basal ganglia, the brain stem and the spinal cord. The neuronal storage material is not sphingomyelin and they are only weakly sudanophilic. Instead, the storage material contains phospholipid and a water-soluble sugar-containing compound.
Spleen: Foamy cells in the spleen contain sphingomyelin and cholesterol and are sudanophilic and positive with ferric hematoxylin. They are also PAS positive in frozen sections.
Liver: Histology varies from near normal to neonatal giant cell hepatitis in the infants presenting with hepatosplenomegaly and severe prolonged obstructive jaundice. Both hepatocytes and Kuffer cells are involved in abnormal storage and they have strong acid phosphatase activity.
Bone marrow: The foamy cells have non-uniform vacuoles and an occasional ingested erythrocyte and often contain densely staining nuclear fragments. They are not sudanophilic, with strong acid phosphatase activity, and stain diffusely with PAS.
Spleen: Storage have features similar to those seen in group I disease.
EM: Neuronal storage has a characteristic appearance and appears as membrane bound polymorphous cytoplasmic bodies, about 3 mm, and contain loosely packed lamellae which are concentric in some planes of sections. Dense osmophilic inclusions are often found.