Efficient Investigation and Differential Diagnosis of Childhood Onset Niemann-Pick Type C

2012 ◽  
Vol 7 (3) ◽  
pp. 153
Author(s):  
Alasdair Parker ◽  
Keyword(s):  
Genetic Testing ◽  
Age Of Onset ◽  
Unmet Need ◽  
Lysosomal Storage ◽  
Cultured Skin ◽  
Specificity And Sensitivity ◽  
Niemann Pick Disease ◽  
History Of ◽  
Type C ◽  
Niemann Pick

Niemann-Pick disease type C (NPC) is a fatal, neurodegenerative, lysosomal storage disorder. It is rare with a broad phenotypic spectrum and variable age of onset. This complicates diagnosis, which is often delayed by several years after presentation of the first symptoms. It is a treatable condition if detected early, therefore reliable means of diagnosis are essential. Clinical diagnosis of NPC involves identifying characteristic neurological features, taking a detailed history of the patient’s details, and must be confirmed by biochemical and/or genetic testing. The key laboratory diagnostic test for NPC is filipin staining of cultured skin fibroblasts, which shows free cholesterol accumulation in lysosomes resulting from impaired intracellular cholesterol transport. Genetic testing for mutations in theNPC1andNPC2genes is also important for confirmation of the diagnosis. However, there is an unmet need for cheaper diagnostic tests with greater specificity and sensitivity

scholarly journals Invariant natural killer T cells are not affected by lysosomal storage in patients with Niemann-Pick disease type C

2012 ◽  
Vol 42 (7) ◽  
pp. 1886-1892 ◽  
Author(s):  
Anneliese O. Speak ◽  
Nicholas Platt ◽  
Mariolina Salio ◽  
Danielle te Vruchte ◽  
David A. Smith ◽  
...  
Keyword(s):  
T Cells ◽  
Natural Killer T Cells ◽  
Disease Type ◽  
Lysosomal Storage ◽  
Niemann Pick Disease ◽  
Type C ◽  
Niemann Pick ◽  
Killer T Cells ◽  
Invariant Natural Killer ◽  
Pick Disease

scholarly journals Human iNSC-derived brain organoid model of lysosomal storage disorder in Niemann–Pick disease type C

2020 ◽  
Vol 11 (12) ◽  
Author(s):  
Seung-Eun Lee ◽  
Nari Shin ◽  
Myung Geun Kook ◽  
Dasom Kong ◽  
Nam Gyo Kim ◽  
...  
Keyword(s):  
Stem Cells ◽  
Lysosomal Storage Disorder ◽  
Disease Type ◽  
Lysosomal Storage ◽  
Niemann Pick Disease ◽  
Type C ◽  
Storage Disorder ◽  
Niemann Pick ◽  
Pick Disease

AbstractRecent studies on developing three-dimensional (3D) brain organoids from stem cells have allowed the generation of in vitro models of neural disease and have enabled the screening of drugs because these organoids mimic the complexity of neural tissue. Niemann-Pick disease, type C (NPC) is a neurodegenerative lysosomal storage disorder caused by mutations in the NPC1 or NPC2. The pathological features underlying NPC are characterized by the abnormal accumulation of cholesterol in acidic compartments, including late endosomes and lysosomes. Due to the inaccessibility of brain tissues from human NPC patients, we developed NPC brain organoids with induced neural stem cells from NPC patient-derived fibroblasts. NPC organoids exhibit significantly reduced size and proliferative ability, which are accompanied by accumulation of cholesterol, impairment in neuronal differentiation, and autophagic flux and dysfunction of lysosomes; therefore, NPC organoids can recapitulate the main phenotypes of NPC patients. Furthermore, these pathological phenotypes observed in NPC organoids were reversed by treatment with valproic acid and HPBCD, which are known to be an effective treatment for several neurodegenerative diseases. Our data present patient-specific phenotypes in 3D organoid-based models of NPC and highlight the application of this model to drug screening in vitro.

scholarly journals Recent neuroimaging, neurophysiological, and neuropathological advances for the understanding of NPC

F1000Research ◽  
2018 ◽  
Vol 7 ◽  
pp. 194 ◽  
Author(s):  
Alberto Benussi ◽  
Maria Sofia Cotelli ◽  
Alessandro Padovani ◽  
Barbara Borroni
Keyword(s):  
Response To Treatment ◽  
The European Union ◽  
Lysosomal Storage ◽  
Niemann Pick Disease ◽  
Disease Staging ◽  
Type C ◽  
Niemann Pick ◽  
New Treatments ◽  
Pick Disease ◽  
Disease Pathways

Niemann–Pick disease type C (NPC) is a rare autosomal recessive lysosomal storage disorder with extensive biological, molecular, and clinical heterogeneity. Recently, numerous studies have tried to shed light on the pathophysiology of the disease, highlighting possible disease pathways common to other neurodegenerative disorders, such as Alzheimer’s disease and frontotemporal dementia, and identifying possible candidate biomarkers for disease staging and response to treatment. Miglustat, which reversibly inhibits glycosphingolipid synthesis, has been licensed in the European Union and elsewhere for the treatment of NPC in both children and adults. A number of ongoing clinical trials might hold promise for the development of new treatments for NPC. The objective of the present work is to review and evaluate recent literature data in order to highlight the latest neuroimaging, neurophysiological, and neuropathological advances for the understanding of NPC pathophysiology. Furthermore, ongoing developments in disease-modifying treatments will be briefly discussed.

scholarly journals A Case Series on Genotype and Outcome of Liver Transplantation in Children with Niemann-Pick Disease Type C

Children ◽  
2021 ◽  
Vol 8 (9) ◽  
pp. 819
Author(s):  
Line Modin ◽  
Vicky Ng ◽  
Paul Gissen ◽  
Julian Raiman ◽  
Eva Doreen Pfister ◽  
...  
Keyword(s):  
Liver Transplantation ◽  
Genetic Testing ◽  
Clinical Presentation ◽  
Case Series ◽  
Presenting Symptoms ◽  
Niemann Pick Disease ◽  
Type C ◽  
Niemann Pick ◽  
Pick Disease

Background: To report on clinical presentation and outcomes of children who underwent liver transplantation (LTx) and were subsequently diagnosed to have Niemann-Pick type C (NPC). Methods: Retrospective, descriptive, multi-centre review of children diagnosed with NPC who underwent LTx (2003–2018). Diagnosis was made by filipin skin test or genetic testing. Results: Nine children were identified (six centres). Neonatal acute liver failure was the most common indication for LTx (seven children). Median age at first presentation: 7 days (range: 0–37). The most prevalent presenting symptoms: jaundice (8/9), hepatosplenomegaly (8/9) and ascites (6/9). 8/9 children had a LTx before the diagnosis of NPC. Genetic testing revealed mutations in NPC1 correlating with a severe biochemical phenotype in 5 patients. All 9 children survived beyond early infancy. Seven children are still alive (median follow-up time of 9 (range: 6–13) years). Neurological symptoms developed in 4/7 (57%) patients at median 9 (range: 5–13) years following LTx. Conclusion: Early diagnosis of NPC continues to be a challenge and a definitive diagnosis is often made only after LTx. Neurological disease is not prevented in the majority of patients. Genotype does not appear to predict neurological outcome after LTx. LTx still remains controversial in NPC.

scholarly journals Biomarkers for Lysosomal Storage Disorders with an Emphasis on Mass Spectrometry

2020 ◽  
Vol 21 (8) ◽  
pp. 2704 ◽  
Author(s):  
Ryuichi Mashima ◽  
Torayuki Okuyama ◽  
Mari Ohira
Keyword(s):  
Mass Spectrometry ◽  
Biomarker Discovery ◽  
Short Review ◽  
Lysosomal Storage Disorders ◽  
Lysosomal Storage ◽  
Niemann Pick Disease ◽  
Clinical Diagnoses ◽  
History Of ◽  
Niemann Pick ◽  
Storage Disorders

Lysosomal storage disorders (LSDs) are characterized by an accumulation of various substances, such as sphingolipids, mucopolysaccharides, and oligosaccharides. The LSD enzymes responsible for the catabolism are active at acidic pH in the lysosomal compartment. In addition to the classically established lysosomal degradation biochemistry, recent data have suggested that lysosome plays a key role in the autophagy where the fusion of autophagosome and lysosome facilitates the degradation of amino acids. A failure in the lysosomal function leads to a variety of manifestations, including neurovisceral disorders. While affected individuals appear to be normal at birth, they gradually become symptomatic in childhood. Biomarkers for each condition have been well-documented and their proper selection helps to perform accurate clinical diagnoses. Based on the natural history of disorders, it is now evident that the existing treatment becomes most effective when initiated during presymptomatic period. Neonatal screening provides such a platform for inborn error of metabolism in general and is now expanding to LSDs as well. These are implemented in some areas and countries, including Taiwan and the U.S. In this short review, we will discuss several issues on some selected biomarkers for LSDs involving Fabry, Niemann–Pick disease type C, mucopolysaccharidosis, and oligosaccharidosis, with a focus on mass spectrometry application to biomarker discovery and detection.

scholarly journals Linear clinical progression, independent of age of onset, in Niemann-Pick disease, type C

2009 ◽  
Vol 9999B ◽  
pp. n/a-n/a ◽  
Author(s):  
Nicole M. Yanjanin ◽  
Jorge I. Vélez ◽  
Andrea Gropman ◽  
Kelly King ◽  
Simona E. Bianconi ◽  
...  
Keyword(s):  
Age Of Onset ◽  
Disease Type ◽  
Clinical Progression ◽  
Niemann Pick Disease ◽  
Type C ◽  
Niemann Pick ◽  
Pick Disease
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