Pathological manifestations of Niemann-Pick type C disease
- meganeurite formation (distortion of neuron shape)
- ectopic dendritogenesis (extensive growth of new ectopic dendrites),2 altering 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 or adult cases of NP-C.3 In addition, amyloid precursor protein (APP) processing is altered, leading to beta-amyloid deposition in the brain.1
Brain atrophy, suggestive of neurodegeneration, is seen in some areas, for example the Purkinje cells of the cerebellum, in patients with particularly slow progressing NP-C or in those with end-stage disease.1,4
Visceral histopathologic features vary considerably in terms of severity and extent. They are characterized by:
- foam cells (lipid-laden macrophages)
- sea-blue histiocytes in the spleen, liver, lung, lymph nodes and bone marrow.5
The most prominent symptom is hepatosplenomegaly, which occurs predominantly in early and late infantile forms of NP-C. Isolated splenomegaly is often present in adulthood and is detected with an abdominal ultrasound.5
There may also be foam cell infiltration of the lungs in infancy, leading to respiratory failure.1,5
- Wraith JE, Imrie J. Understanding Niemann-Pick disease type C and its potential treatment. UK Blackwell Publishing, 2007.
- Zervas M, Dobrenis K, Walkley S. Neurons in Niemann-Pick disease type C accumulate gangliosides as well as unesterified cholesterol and undergo dendritic and axonal alterations. J Neuropathol Exp Neurol 2001;60:49-64.
- Suzuki K, Parker CC, Pentchev PG, et al. Neurofibrillary tangles in Niemann-Pick disease type C. Acta Neuropathol 1995;89:227-38
- Walkley SU. Cellular pathology of lysosomal storage disorders Brain Pathol 1998;8:175-193.
- Patterson MC, Vanier MT, Suzuki K, et al. Niemann-Pick disease, type C: a lipid trafficking disorder. In: Scriver CR, Beaudet AL, Sly WS, Valle D, Childs B, Vogelstein B (eds) The Metabolic and Molecular Bases of Inherited Disease, 8th ed, 2001. New York: McGraw-Hill, Ch 145, pp 3611-33.