Niemann-Pick Disease Type D (NPD-D), also known as Niemann-Pick Disease Type C1-like (NPC1L1), is a rare and progressive genetic disorder characterized by the accumulation of lipids, primarily cholesterol and glycosphingolipids, within the cells of various organs, particularly the brain. It is caused by mutations in the NPC1-like1 protein (NPC1L1) gene.
Individuals with NPD-D typically develop symptoms during childhood or adolescence, although the age of onset and disease severity can vary greatly. Initial signs often involve hepatosplenomegaly (enlarged liver and spleen), which may cause abdominal discomfort and respiratory difficulties. Neurological symptoms tend to appear later and may include ataxia (lack of muscle coordination), dystonia (involuntary muscle contractions), developmental delay, seizures, and progressive cognitive impairment.
The accumulation of lipids within cells leads to the dysfunction of various organ systems such as the liver, lungs, and central nervous system. As a result, affected individuals may experience respiratory problems, hearing loss, impaired motor function, and progressive neurodegeneration.
NPD-D is inherited in an autosomal recessive manner, meaning that an affected individual must inherit two mutated copies of the NPC1L1 gene, one from each parent. The disease is extremely rare, with an estimated prevalence of less than 1 in 1,000,000 individuals worldwide.
While there is currently no cure for NPD-D, management focuses on symptom relief and supportive care. Various treatments, including enzyme replacement therapy, substrate reduction therapy, and miglustat (a pharmacological chaperone), are being investigated to potentially improve the quality of life for individuals affected by the disease. Genetic counseling is also crucial
