- PMID
- Gene Name
- Molecular Event
- Function in UC
- 19744920
- NPC1
- mutation
- Diagnosis
- Method
- NA
- Summary
- Niemann-Pick type C1 disease (NPC1) is an autosomal recessive lysosomal storage disorder characterized by Neonatal jaundice and suggest plasma HDL-C represents a potential biomarker of NPC1 disease severity.
- The National Niemann-Pick Type C1 Disease Database: correlation of lipid profiles, mutations, and biochemical phenotypes. Journal of lipid research, 2010 Feb [Go to PubMed]
- Niemann-Pick type C1 disease (NPC1) is an autosomal recessive lysosomal storage disorder characterized by neonatal jaundice, hepatosplenomegaly, and progressive neurodegeneration. The present study provides the lipid profiles, mutations, and corresponding associations with the biochemical phenotype obtained from NPC1 patients who participated in the National NPC1 Disease Database. Lipid profiles were obtained from 34 patients (39%) in the survey and demonstrated significantly reduced plasma LDL cholesterol (LDL-C) and increased plasma triglycerides in the majority of patients. Reduced plasma HDL cholesterol (HDL-C) was the most consistent lipoprotein abnormality found in male and female NPC1 patients across age groups and occurred independent of changes in plasma triglycerides. A subset of 19 patients for whom the biochemical severity of known NPC1 mutations could be correlated with their lipid profile showed a strong inverse correlation between plasma HDL-C and severity of the biochemical phenotype. Gene muations were available for 52 patients (59%) in the survey, including 52 different mutations and five novel mutations (Y628C, P887L, I923V, A1151T, and 3741_3744delACTC). Together, these findings provide novel information regarding the plasma lipoprotein changes and mutations in NPC1 disease, and suggest plasma HDL-C represents a potential biomarker of NPC1 disease severity.
- 23146215
- NPC1
- mutation
- Diagnosis; Pathogenesis
- Method
- NA
- Summary
- This case demonstrates the importance of effective seizure control therapy in achieving and maintaining neurological stabilization in Niemann-Pick disease type C.
- Use of miglustat in a child with late-infantile-onset Niemann-Pick disease type C and frequent seizures: a case report. Journal of medical case reports, 2012 [Go to PubMed]
- Niemann-Pick disease type C is a rare genetic lysosomal storage disease associated with impaired intracellular lipid trafficking and a range of progressive neurological manifestations. The influence of seizure activity on disease course and response to miglustat therapy is not currently clear.
Niemann-Pick disease type C homozygous for NPC1 mutation p.S940L [c. 2819 C>T] was diagnosed in a four-and-a-half-year-old Norwegian Caucasian girl. The patient, who died at eight years and seven months of age, had a history of prolonged neonatal jaundice and subsequently displayed progressive neurological manifestations that started with delayed speech, ataxia, and gelastic cataplexy. A regimen of 100mg of miglustat three times a day was initiated when she was four years and 11 months old. She showed decreased neurological deterioration during about three and a half years of treatment. However, she displayed periods of distinct worsening that coincided with frequent epileptic seizures. Anti-epileptic therapy reduced seizure frequency and severity and allowed re-stabilization of her neurological function. Prior to her death, which was possibly due to acute cardiac arrest, seizure activity was well controlled.
Miglustat delayed the expected deterioration of neurological function in this patient with p.S940L-homozygous late-infantile-onset Niemann-Pick disease type C and provided important quality-of-life benefits. This case demonstrates the importance of effective seizure control therapy in achieving and maintaining neurological stabilization in Niemann-Pick disease type C. - 18438776
- NPC1
- mutation
- Diagnosis; Pathogenesis
- Method
- NA
- Summary
- This novel NPC1 antisense mouse model will allow delineation of the mechanism by which NPC1 dysfunction leads to liver cell death.
- In vivo antisense oligonucleotide reduction of NPC1 expression as a novel mouse model for Niemann Pick type C- associated liver disease. Hepatology (Baltimore, Md.), 2008 May [Go to PubMed]
- Niemann-Pick type C (NPC) is a fatal autosomal recessive lipidosis that is characterized by lysosomal storage of cholesterol and glycosphingolipids. Patients exhibit prolonged neonatal jaundice, hepatosplenomegaly, and progressive neurodegeneration that generally result in death by the teen years. Most clinical cases are caused by mutations in the NPC1 gene. Current mouse models of NPC are not well suited for studying the liver disease due to the rapidly progressing neurological disease. To facilitate study of NPC-associated liver dysfunction, we have developed a novel mouse model using antisense oligonucleotides to ablate NPC1 expression primarily in the liver. Here, we show that the NPC1 knockdown leads to a liver disease phenotype similar to that of patients with NPC and the NPC(nih) mouse model. Key features include hepatomegaly, lipid storage, elevated serum liver enzymes, and increased apoptosis.
This novel NPC1 antisense mouse model will allow delineation of the mechanism by which NPC1 dysfunction leads to liver cell death.
3 pubmed articles have reported NPC1 mutation associated with Neonatal Jaundice.