[citation needed] Accumulation of sphingomyelin in the central nervous system (including the cerebellum) results in unsteady gait (ataxia), slurring of speech (dysarthria), and difficulty swallowing (dysphagia).

Upper brainstem disease results in impaired voluntary rapid eye movements (supranuclear gaze palsy).

[citation needed] In the classic infantile type-A variant, a missense mutation causes complete deficiency of sphingomyelinase.

Numerous small vacuoles of relatively uniform size are created, giving the cytoplasm a foamy appearance.

To diagnose type C, a skin sample can help determine whether the transporter is affected via the Filipin test which detects build-up of unesterified cholesterol via fluorescent staining.

Type A patients exhibit hepatosplenomegaly in infancy and profound central nervous system involvement and are unable to survive beyond two years of age.

Type B patients also show hepatosplenomegaly and pathologic alterations of their lungs, but usually without the involvement of their central nervous system.

Some can develop significant life-threatening complications, including liver failure, hemorrhage, oxygen dependency, pulmonary infections, and splenic rupture.

If the spleen is enlarged and platelet levels low, acute episodes of bleeding may require transfusions of blood products.

[8] In January 2009, miglustat (Zavesca) was authorized in the European Union for the treatment of progressive neurological manifestations in people with Niemann-Pick type C disease.

In March 2010, the US Food and Drug Administration (FDA) requested additional pre-clinical and clinical information regarding miglustat from Actelion before making a final decision on approving it in the United States for Niemann-Pick type C disease.

[28] Curiously, in 2011 fibroblast cells derived from patients with Niemann–Pick type C1 disease were shown to be resistant to Ebola virus because of mutations in the NPC1 protein, which is needed for viral escape from the vesicular compartment.

[35] Researchers noted that HPBCDs, with varying levels of 2-hydroxypropyl substitution, had effects in delaying neurological symptoms and in decreasing liver cholesterol storage in a Niemann–Pick mouse model.

[36] In April 2011, the U.S. National Institutes of Health, in collaboration with the Therapeutics for Rare and Neglected Diseases Program,[37] announced they were developing a clinical trial using HPbCD for Niemann–Pick type C1 patients.

It has been used preclinically, in a mouse model of Niemann–Pick type C, using an adeno-associated virus-derived viral vector, and has been shown to extend lifespan following injection into the lateral ventricles of the neonatal brain.

[40] In a separate proof-of-concept study, a similar vector, but with a modified capsid, was injected intravenously into Niemann–Pick type C mice around four weeks of age; this resulted in extended lifespan and improved weight gain.

[41] Gene therapy has also been used preclinically in a mouse model of Niemann–Pick type A. Injection into the cisterna magna at seven weeks of age prevented motor and memory impairment and neuronal cell death.