Niemann–Pick disease type C

Protein NPC1 PDB 3GKH

Niemann–Pick disease type C (NPC) is a lysosomal storage disorder that affects the body's ability to transport cholesterol and other lipids inside of cells. This leads to an accumulation of these substances within various tissues, causing a range of symptoms and complications.

Classification

Niemann–Pick disease type C is one of several types of Niemann–Pick disease, which are classified based on the specific genetic mutations and the resulting biochemical abnormalities. NPC is distinct from Niemann–Pick disease type A and Niemann–Pick disease type B, which are caused by mutations in the SMPD1 gene.

Genetics

NPC is an autosomal recessive disorder, meaning that an individual must inherit two copies of the defective gene, one from each parent, to develop the disease. The majority of NPC cases are caused by mutations in the NPC1 gene, while a smaller number are due to mutations in the NPC2 gene. These genes are responsible for producing proteins that are essential for the normal transport of cholesterol and lipids within cells.

Pathophysiology

The defective proteins in NPC lead to the accumulation of cholesterol and other lipids in the lysosomes of cells. This accumulation disrupts normal cellular function and leads to the progressive damage of various tissues, particularly the central nervous system, liver, and spleen.

Symptoms

The symptoms of NPC can vary widely and may include:

• Hepatosplenomegaly (enlarged liver and spleen)
• Jaundice in newborns
• Ataxia (loss of coordination)
• Dysarthria (difficulty speaking)
• Dysphagia (difficulty swallowing)
• Seizures
• Dementia
• Vertical supranuclear gaze palsy (difficulty moving the eyes up and down)

Diagnosis

Diagnosis of NPC typically involves a combination of clinical evaluation, family history, and specialized tests. These tests may include:

• Filipin staining of skin cells to detect cholesterol accumulation
• Genetic testing to identify mutations in the NPC1 or NPC2 genes
• Biochemical assays to measure cholesterol and lipid levels in cells

Treatment

There is currently no cure for NPC, but treatment focuses on managing symptoms and slowing disease progression. Therapies may include:

• Miglustat, a drug that inhibits the synthesis of glycosphingolipids
• Supportive care, such as physical therapy, speech therapy, and nutritional support
• Experimental treatments, including gene therapy and other investigational drugs

Prognosis

The prognosis for individuals with NPC varies depending on the severity of the disease and the age of onset. Early-onset forms of NPC tend to be more severe and progress more rapidly, while later-onset forms may have a slower progression. Lifespan can be significantly shortened, particularly in severe cases.

Research

Ongoing research is focused on better understanding the molecular mechanisms of NPC, developing new diagnostic tools, and finding effective treatments. Clinical trials are being conducted to evaluate the safety and efficacy of potential therapies.

See also

• Lysosomal storage disorder
• Niemann–Pick disease
• Cholesterol metabolism
• Genetic disorder