Niemann-Pick disease, type C

=Niemann-Pick Disease, Type C = Niemann-Pick Disease, Type C (NPC) is a rare, inherited, neurodegenerative disorder characterized by an inability of the body to transport cholesterol and other lipids inside of cells. This leads to an accumulation of these substances within various tissues of the body, including the brain, liver, and spleen.

Pathophysiology

NPC is caused by mutations in either the NPC1 or NPC2 genes. These genes are responsible for producing proteins that are essential for the normal transport of cholesterol and lipids within cells. Mutations in these genes disrupt this process, leading to the accumulation of lipids in the lysosomes, which are cellular organelles responsible for breaking down waste materials.

NPC1 and NPC2 Genes

• NPC1 is located on chromosome 18 and encodes a protein that is involved in the transport of cholesterol from lysosomes to other parts of the cell.
• NPC2 is located on chromosome 14 and encodes a small soluble protein that binds cholesterol and is thought to work in conjunction with NPC1 to facilitate cholesterol transport.

Clinical Features

The symptoms of NPC can vary widely among affected individuals and can present at any age from infancy to adulthood. Common symptoms include:

• Hepatosplenomegaly (enlarged liver and spleen)
• Ataxia (lack of muscle coordination)
• Dysarthria (difficulty speaking)
• Dysphagia (difficulty swallowing)
• Vertical supranuclear gaze palsy (difficulty moving the eyes up and down)
• Progressive neurological decline

Diagnosis

Diagnosis of NPC can be challenging due to the variability of symptoms. It typically involves a combination of clinical evaluation, genetic testing, and biochemical assays. The following tests may be used:

• Filipin staining to detect cholesterol accumulation in skin fibroblasts.
• Genetic testing to identify mutations in the NPC1 or NPC2 genes.

Treatment

Currently, there is no cure for NPC, but treatments are available to manage symptoms and slow disease progression. These include:

• Miglustat, a drug that may help reduce the accumulation of lipids.
• Supportive therapies such as physical therapy, speech therapy, and nutritional support.

Research and Future Directions

Research is ongoing to better understand NPC and develop new treatments. Areas of focus include:

• Gene therapy to correct the underlying genetic defect.
• Small molecule drugs to enhance cholesterol transport.

See Also

• Lysosomal storage disorders
• Cholesterol metabolism

External Links

• National Niemann-Pick Disease Foundation
• Genetic and Rare Diseases Information Center

NIH genetic and rare disease info

• NIH info on Niemann-Pick disease, type C

Niemann-Pick disease, type C is a rare disease.