scholarly journals Peripheral neuropathy as a very rare symptom in a patient with Niemann–Pick type C with negative enzymatic evaluation: a case report

2022 ◽  
Vol 16 (1) ◽  
Author(s):  
Mohammad Barzegar ◽  
Fatemeh Valaee ◽  
Shadi Ghoreishizadeh
Keyword(s):  
Peripheral Neuropathy ◽  
Rare Complication ◽  
Failure To Thrive ◽  
Lysosomal Storage ◽  
Enzymatic Function ◽  
Elevated Liver Enzymes ◽  
Physical Abilities ◽  
Type C ◽  
Niemann Pick ◽  
Rare Symptom

Abstract Background Niemann–Pick is a rare metabolic disease distinguished by lysosomal storage defects. This disease is characterized by sphingomyelinase acid deficiency, causing its accumulation in various organs such as the kidneys, spleen, liver, brain, and nerves. Niemann–Pick disease is categorized into four groups: A, B, C, and D. Peripheral neuropathy is an extremely rare complication in patients with Niemann–Pick type C, which certainly leads to neurologic deterioration. Case presentation We report a case of Niemann–Pick type C disease in a 3-year-old Iranian Azeri female patient who was hospitalized twice. The first time was at 1 month of age with symptoms of splenomegaly, jaundice, and elevated liver enzymes, and the second time was at around age 2 for loss of mental and physical abilities. The patient presented with failure to thrive. According to paraclinical examinations, mildly delayed myelination along with a nonspecific periventricular hypersignal intensity was seen. Interestingly, the patient’s Niemann–Pick type C enzymatic function was evaluated twice and was negative on both occasions, while she was positive for NPC1 and NPC2 gene examinations. Conclusions In this study, despite the enzymatic study being negative, Niemann–Pick type C disease was finally confirmed, revealing the importance of mutations in Niemann–Pick type C pathogenesis. Besides, peripheral neuropathy was diagnosed in this patient as a very rare symptom of Niemann–Pick type C.

scholarly journals Case Report: Ursodeoxycholic acid treatment in Niemann-Pick disease type C; clinical experience in four cases

2017 ◽  
Vol 2 ◽  
pp. 75 ◽  
Author(s):  
William R.H. Evans ◽  
Elena-Raluca Nicoli ◽  
Raymond Y. Wang ◽  
Nina Movsesyan ◽  
Frances M. Platt
Keyword(s):  
Bile Acid ◽  
Ursodeoxycholic Acid ◽  
Liver Enzyme ◽  
Liver Dysfunction ◽  
Case Series ◽  
Later Life ◽  
Lysosomal Storage ◽  
Elevated Liver Enzymes ◽  
Type C ◽  
Niemann Pick

In this case series, we demonstrate that Ursodeoxycholic acid (UDCA) improves liver dysfunction in Niemann-Pick type C (NPC) and may restore a suppressed cytochrome p450 system. NPC disease is a progressive neurodegenerative lysosomal storage disease caused by mutations in either the NPC1 or NPC2 genes. Liver disease is a common feature presenting either acutely as cholestatic jaundice in the neonatal period, or in later life as elevated liver enzymes indicative of liver dysfunction. Recently, an imbalance in bile acid synthesis in a mouse model of NPC disease was linked to suppression of the P450 detoxification system and was corrected by UDCA treatment. UDCA (3α, 7β-dihydroxy-5β-cholanic acid), a hydrophilic bile acid, is used to treat various cholestatic disorders. In this report we summarise the findings from four independent cases of NPC, three with abnormal liver enzyme levels at baseline, that were subsequently treated with UDCA. The patients differed in age and clinical features, they all tolerated the drug well, and in those with abnormal liver function, there were significant improvements in their liver enzyme parameters.

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.

Niemann-pick type C disease associated with peripheral neuropathy

2003 ◽  
Vol 29 (3) ◽  
pp. 242-244 ◽  
Author(s):  
Dimitrios I Zafeiriou ◽  
Panagiota Triantafyllou ◽  
Nikolaos P Gombakis ◽  
Euthymia Vargiami ◽  
Chaido Tsantali ◽  
...  
Keyword(s):  
Peripheral Neuropathy ◽  
Type C ◽  
Niemann Pick

scholarly journals The Lysosome: A Potential Therapeutic Juncture between the COVID-19 Pandemic and Niemann-Pick Type C Disease

2020 ◽  
Author(s):  
Rami Ballout
Keyword(s):  
Mechanisms Of Action ◽  
Comparable Efficacy ◽  
Lysosomal Storage ◽  
Viral Propagation ◽  
Lysosomal Dysfunction ◽  
The World ◽  
The Face ◽  
Type C ◽  
Niemann Pick ◽  
Storage Disorders

In the face of the newly emergent COVID-19 pandemic, researchers around the world are racing to identify efficacious drugs capable of preventing or treating its infection. They are doing that by testing already available and approved antimicrobials for their rapid repurposing against COVID-19. Using the data emerging on the comparable efficacy of various compounds having different mechanisms of action and indications, I suggest in this report, their potential mechanistic convergence. Specifically, I highlight the lysosome as a key possible therapeutic target for COVID-19, proposing one of the lysosomal storage disorders, Niemann-Pick type C disease (NPC), as a prototypical condition with inherent resistance or an “unfavorable” host cell environment for viral propagation. The included reasoning evolves from previously generated data in NPC, along with the emerging data on COVID-19. The aim of this report is to suggest that pharmacological induction of a “transient” NPC-like lysosomal dysfunction, could hold answers for targeting the ongoing COVID-19 pandemic.

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 Proteomic Analysis of Niemann-Pick Type C Hepatocytes Reveals Potential Therapeutic Targets for Liver Damage

Cells ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 2159
Author(s):  
Elisa Balboa ◽  
Tamara Marín ◽  
Juan Esteban Oyarzún ◽  
Pablo S. Contreras ◽  
Robert Hardt ◽  
...  
Keyword(s):  
Liver Damage ◽  
Therapeutic Targets ◽  
Bioinformatic Analysis ◽  
P Value ◽  
Lysosomal Storage ◽  
Npc1 Gene ◽  
The Central Nervous System ◽  
Type C ◽  
Niemann Pick ◽  
Lysosomal Proteins

Niemann-Pick type C disease (NPCD) is a lysosomal storage disorder caused by mutations in the NPC1 gene. The most affected tissues are the central nervous system and liver, and while significant efforts have been made to understand its neurological component, the pathophysiology of the liver damage remains unclear. In this study, hepatocytes derived from wild type and Npc1−/− mice were analyzed by mass spectrometry (MS)-based proteomics in conjunction with bioinformatic analysis. We identified 3832 proteins: 416 proteins had a p-value smaller than 0.05, of which 37% (n = 155) were considered differentially expressed proteins (DEPs), 149 of them were considered upregulated, and 6 were considered downregulated. We focused the analysis on pathways related to NPC pathogenic mechanisms, finding that the most significant changes in expression levels occur in proteins that function in the pathways of liver damage, lipid metabolism, and inflammation. Moreover, in the group of DEPs, 30% (n = 47) were identified as lysosomal proteins and 7% (n = 10) were identified as mitochondrial proteins. Importantly, we found that lysosomal DEPs, including CTSB/D/Z, LIPA, DPP7 and GLMP, and mitocondrial DEPs, AKR1B10, and VAT1 had been connected with liver fibrosis, damage, and steatosis in previous studies, validiting our dataset. Our study found potential therapeutic targets for the treatment of liver damage in NPCD.

scholarly journals Release of acidic store calcium is required for effective priming of the NLRP3 inflammasome

2022 ◽  
Author(s):  
Nick Platt ◽  
Dawn Shepherd ◽  
Yuzhe Weng ◽  
Grant Charles Churchill ◽  
Antony Galione ◽  
...  
Keyword(s):  
Nlrp3 Inflammasome ◽  
Calcium Release ◽  
Inflammatory Responses ◽  
Lysosomal Storage ◽  
Release Channel ◽  
Type C ◽  
Niemann Pick ◽  
Lysosomal Protein

The lysosome is a dynamic signaling organelle that is critical for cell functioning. It is a regulated calcium store that can contribute to Ca2+-regulated processes via both local calcium release and more globally by influencing ER Ca2+release. Here, we provide evidence from studies of an authentic mouse model of the lysosomal storage disease Niemann-Pick Type C (NPC) that has reduced lysosomal Ca2+ levels, and genetically modified mice in which the two-pore lysosomal Ca2+ release channel family are deleted that lysosomal Ca2+ signaling is required for normal pro-inflammatory responses. We demonstrate that production of the pro-inflammatory cytokine IL-1beta via the NLRP3 inflammasome is significantly reduced in murine Niemann-Pick Type C, the inhibition is selective because secretion of TNF alpha is not diminished, and it is a consequence of inefficient inflammasome priming. Synthesis of precursor ProIL-1 beta is significantly reduced in macrophages genetically deficient in the lysosomal protein Npc1, which is mutated in most clinical cases of NPC, and in wild type cells in which Npc1 activity is pharmacologically inhibited. Comparable reductions in ProIL-1 beta generation were measured in vitro and in vivo by macrophages genetically altered to lack expression of the two-pore lysosomal Ca2+ release channels Tpcn1 or Tpcn2. These data demonstrate a requirement for lysosome-dependent Ca2+ signaling in the generation of specific pro-inflammatory responses.

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