The NPC1 gene encodes a protein that is located in membranes inside the cell and is involved in the movement of cholesterol and lipids within cells. A deficiency of this protein leads to the abnormal buildup of lipids and cholesterol within cell membranes. The NPC2 gene encodes a protein that binds and transports cholesterol. It has been shown to closely interact with NPC1. "Type D" variant
Type D Niemann–Pick has only been found in the French Canadian population of Yarmouth County, Nova Scotia, and is now known to be allelic with Niemann–Pick type C.
Genealogical research indicates that Joseph Muise (c. 1679–1729) and Marie Amirault (1684 – c. 1735) are common ancestors to all people with Type D. This couple is the most likely origin for the type D variant. Pathophysiology
Niemann–Pick type C is biochemically, genetically and clinically distinct from Niemann–Pick Types A or and B. In Types A and B, there is complete or partial deficiency of the lysosomal enzyme called acid sphingomyelinase. In Niemann–Pick type C, the protein product of the major mutated gene NPC1 is not an enzyme but appears to function as a transporter in the endosomal-lysosomal system, which moves large water-insoluble molecules through the cell. The protein coded by the NPC2 gene more closely resembles an enzyme structurally but seems to act in cooperation with the NPC1 protein in transporting molecules in the cell. The disruption of this transport system results in the accumulation of cholesterol and glycolipids in lysosomes.Cholesterol and glycolipids have varied roles in the cell.
Fetal trimethadione syndrome (also known as paramethadione syndrome, German syndrome, tridione syndrome, among others) is a set of birth defects caused by the administration of the anticonvulsants trimethadione (also known as Tridione) or paramethadione to epileptic mothers during pregnancy.Fetal trimethadione syndrome is classified as a rare disease by the National Institute of Healths Office of Rare Diseases, meaning it affects less than 200,000 individuals in the United States.The fetal loss rate while using trimethadione has been reported to be as high as 87%. Presentation
Fetal trimethadione syndrome is characterized by the following major symptoms as a result of the teratogenic characteristics of trimethadione. Cranial and facial abnormalities which include; microcephaly, midfacial flattening, V-shaped eyebrows and a short nose
Cardiovascular abnormalities
Absent kidney and ureter
Meningocele, a birth defect of the spine
Omphalocele, a birth defect where portions of the abdominal contents project into the umbilical cord
A delay in mental and physical development

Diagnosis
Treatment
Surgery may help alleviate the effects of some physical defects, but prognosis is poor, especially for those with severe cardiovascular and cognitive problems. Speech and physical therapy, as well as special education is required for surviving children. References


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