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Pathological manifestations of Niemann-Pick type C disease

Neuropathology
In Niemann-Pick type C disease (NP-C) lipids accumulate in neurons and glial cells, causing neuropathological changes, including: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 pathology
Visceral histopathologic features vary considerably in terms of severity and extent. They are characterized by:


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

References

  1. Wraith JE, Imrie J. Understanding Niemann-Pick disease type C and its potential treatment. UK Blackwell Publishing, 2007.
  2. 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.
  3. Suzuki K, Parker CC, Pentchev PG, et al. Neurofibrillary tangles in Niemann-Pick disease type C. Acta Neuropathol 1995;89:227-38
  4. Walkley SU. Cellular pathology of lysosomal storage disorders Brain Pathol 1998;8:175-193.
  5. 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.