Pathological manifestations of Niemann-Pick type C disease

Neuropathology

In Niemann-Pick type C disease (NP-C) lipid accumulation is observed in neurons and glial cells.¹ Lipid build up, especially glycosphingolipids, causes neuropathological changes including meganeurite formation (distortion of neuron shape) and ectopic dendritogenesis (extensive growth of new ectopic dendrites).¹ Ectopic dendritogenesis alters neurotransmission leading to the neurological symptoms of NP-C.¹

Neurofibrillary tangles (NFTs), a feature of Alzheimer's disease, are found in the basal ganglia, hypothalamus, brain stem and spinal cord of most juvenile/adult cases of NP-C.^1,2,3 Furthermore, in NP-C the processing of amyloid precursor protein (APP) is altered leading to beta-amyloid deposition in the brain, as is observed in Alzheimer's disease.¹

Additionally, brain atrophy, suggesting neurodegeneration, is seen in some areas of the brain (e.g. Purkinje cells of the cerebellum) in patients with end-stage, or particularly slow progressing NP-C.¹

Visceral pathology

Visceral histopathologic features vary considerably in severity and extent but are characterized by foam cells (lipid-laden macrophages) and sea-blue histiocytes in the spleen, liver, lung, lymph nodes and bone marrow.¹ The most prominent symptom is hepatosplenomegaly , which mostly occurs in infants.¹ Some infants with NP-C may experience infiltration of the lungs with foam cells leading to respiratory failure.^1,4

References

1. Wraith JE, Imrie J. Understanding Niemann-Pick disease type C and its potential treatment. UK Blackwell Publishing, 2007.
2. Suzuki K, Parker CC, Pentchev PG et al. Neurofibrillary tangles in Niemann-Pick disease type C. Acta Neuropathol (Berl) 1995;89:227-38.
3. Patterson MC. A riddle wrapped in a mystery: understanding Niemann-Pick disease, type C. Neurologist 2003;9:301-10.
4. Patterson MC. Niemann-Pick disease Type C. Gene Reviews 2007a (updated 9 July). Accessible at: www.geneclinics.org. Accessed October 2008.