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