Niemann-Pick Disease Type C with Isolated Splenomegaly: A Case Report in a Child

2021 ◽  
Author(s):  
Bruna Ribeiro Torres ◽  
Daniela Otoni Russo ◽  
Vinícius Andrade Gomes Vuolo ◽  
Tarcísio Silva Borborema ◽  
André Vinícius Soares Barbosa ◽  
...  
Keyword(s):  
Autosomal Recessive Inheritance ◽  
Signs And Symptoms ◽  
Disease Type ◽  
Sphingolipid Metabolism ◽  
Neurological Involvement ◽  
Lysosomal Storage ◽  
Niemann Pick Disease ◽  
Type C ◽  
Niemann Pick ◽  
Pick Disease

AbstractNiemann-Pick disease type C is an innate error of lysosomal storage metabolism with an autosomal recessive inheritance pattern. The disease causes intracellular cholesterol accumulation and changes in sphingolipid metabolism. If cholesterol accumulates, the signs and symptoms of visceral involvement predominate. Neurological involvement results from sphingolipid accumulation. A 7-year-old student was referred to a tertiary service for the investigation of asymptomatic splenomegaly. Following an extensive examination, he was diagnosed with Niemann-Pick disease type C. Interestingly, this case's only symptom was splenomegaly.

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 Inhibition of GM3 Synthase Attenuates Neuropathology of Niemann-Pick Disease Type C by Affecting Sphingolipid Metabolism

2014 ◽  
Vol 37 (2) ◽  
pp. 161-171 ◽  
Author(s):  
Hyun Lee ◽  
Jong Kil Lee ◽  
Yong Chul Bae ◽  
Song Hyun Yang ◽  
Nozomu Okino ◽  
...  
Keyword(s):  
Disease Type ◽  
Sphingolipid Metabolism ◽  
Gm3 Synthase ◽  
Niemann Pick Disease ◽  
Type C ◽  
Niemann Pick ◽  
Pick Disease

scholarly journals Differential response of the liver to bile acid treatment in a mouse model of Niemann-Pick disease type C

2017 ◽  
Vol 2 ◽  
pp. 76 ◽  
Author(s):  
Elena-Raluca Nicoli ◽  
David Smith ◽  
Lauren Morris ◽  
Frances M. Platt
Keyword(s):  
Bile Acid ◽  
Mouse Model ◽  
Acid Treatment ◽  
Disease Type ◽  
Lysosomal Storage ◽  
Niemann Pick Disease ◽  
Type C ◽  
Niemann Pick ◽  
Cholanic Acid ◽  
Pick Disease

Niemann-Pick disease type C (NPC) disease is a neurodegenerative lysosomal storage disease caused by mutations in the NPC1 or NPC2 genes. Liver disease is also a common feature of NPC that can present as cholestatic jaundice in the neonatal period. Liver enzymes can remain elevated above the normal range in some patients as they age. We recently reported suppression of the P450 detoxification system in a mouse model of NPC disease and in post-mortem liver from NPC patients. As bile acids regulate the P450 system, we tested bile acid treatment using ursodeoxycholic acid (UDCA; 3α, 7β-dihydroxy-5β-cholanic acid), a hydrophilic bile acid, which is used to treat several cholestatic disorders. In this study, we compared UDCA treatment with the bile acid cholic acid (CA), and found unexpected hepatotoxicity in response to CA in Npc1 mice, but not to UDCA, suggesting that only UDCA should be used as an adjunctive therapy in NPC patients.

scholarly journals Recommendations for the detection and diagnosis of Niemann-Pick disease type C

2017 ◽  
Vol 7 (6) ◽  
pp. 499-511 ◽  
Author(s):  
Marc C. Patterson ◽  
Peter Clayton ◽  
Paul Gissen ◽  
Mathieu Anheim ◽  
Peter Bauer ◽  
...  
Keyword(s):  
Clinical Practice ◽  
Diagnostic Algorithm ◽  
Signs And Symptoms ◽  
Disease Type ◽  
Niemann Pick Disease ◽  
Substantial Progress ◽  
Type C ◽  
Detection And Diagnosis ◽  
Niemann Pick ◽  
Pick Disease

AbstractPurpose of review:Niemann-Pick disease type C (NP-C) is a neurovisceral disorder that may be more prevalent than earlier estimates. Diagnosis of NP-C is often delayed; a key aim for clinical practice is to reduce this delay. Recently, substantial progress has been made in the field of NP-C screening and diagnosis, justifying an update to the existing recommendations for clinical practice.Recent findings:New biomarker profiling and genetic analysis technologies are included as first-line diagnostic tests for NP-C. Most diagnoses can now be confirmed by combination of biomarker and genetic analyses. Filipin staining may facilitate diagnosis in uncertain cases. Recommendations are provided for psychiatrists, neuro-ophthalmologists, and radiologists, and on screening within specific at-risk patient cohorts. The NP-C diagnostic algorithm has been updated and simplified.Summary:This publication provides expert recommendations for clinicians who may see patients presenting with the signs and symptoms of NP-C, including general practitioners, pediatricians, neurologists, and psychiatrists.

scholarly journals Differential response of the liver to bile acid treatment in a mouse model of Niemann-Pick disease type C

2018 ◽  
Vol 2 ◽  
pp. 76
Author(s):  
Elena-Raluca Nicoli ◽  
Mylene Huebecker ◽  
David Smith ◽  
Lauren Morris ◽  
Frances M. Platt
Keyword(s):  
Bile Acid ◽  
Mouse Model ◽  
Disease Type ◽  
Lysosomal Storage ◽  
Niemann Pick Disease ◽  
Type C ◽  
Niemann Pick ◽  
Npc Mouse ◽  
Cholanic Acid ◽  
Pick Disease

Niemann-Pick disease type C (NPC) disease is a neurodegenerative lysosomal storage disease caused by mutations in the NPC1 or NPC2 genes. Liver disease is also a common feature of NPC that can present as cholestatic jaundice in the neonatal period. Liver enzymes can remain elevated above the normal range in some patients as they age. We recently reported suppression of the P450 detoxification system in a mouse model of NPC disease and also in post-mortem liver from NPC patients. We demonstrated the ability of the hydrophobic bile acid ursodeoxycholic acid (UDCA) (3α, 7β-dihydroxy-5β-cholanic acid) to correct the P450 system suppression. UDCA is used to treat several cholestatic disorders and was tested in NPC due to the P450 system being regulated by bile acids. Here, we compare the effect of UDCA and cholic acid (CA), another bile acid, in the NPC mouse model. We observed unexpected hepatotoxicity in response to CA treatment of NPC mice. No such hepatotoxicity was associated with UDCA treatment. These results suggest that CA treatment is contraindicated in NPC patients, whilst supporting the use of UDCA as an adjunctive therapy in NPC patients.

scholarly journals Unbiased yeast screens identify cellular pathways affected in Niemann–Pick disease type C

2020 ◽  
Vol 3 (7) ◽  
pp. e201800253
Author(s):  
Alexandria Colaco ◽  
María E Fernández-Suárez ◽  
Dawn Shepherd ◽  
Lihi Gal ◽  
Chen Bibi ◽  
...  
Keyword(s):  
Metal Ion ◽  
Ion Homeostasis ◽  
Disease Type ◽  
Nutrient Sensing ◽  
Lysosomal Storage ◽  
Metal Ion Homeostasis ◽  
Niemann Pick Disease ◽  
Type C ◽  
Niemann Pick ◽  
Pick Disease

Niemann–Pick disease type C (NPC) is a rare lysosomal storage disease caused by mutations in either the NPC1 or NPC2 genes. Mutations in the NPC1 gene lead to the majority of clinical cases (95%); however, the function of NPC1 remains unknown. To gain further insights into the biology of NPC1, we took advantage of the homology between the human NPC1 protein and its yeast orthologue, Niemann–Pick C–related protein 1 (Ncr1). We recreated the NCR1 mutant in yeast and performed screens to identify compensatory or redundant pathways that may be involved in NPC pathology, as well as proteins that were mislocalized in NCR1-deficient yeast. We also identified binding partners of the yeast Ncr1 orthologue. These screens identified several processes and pathways that may contribute to NPC pathogenesis. These included alterations in mitochondrial function, cytoskeleton organization, metal ion homeostasis, lipid trafficking, calcium signalling, and nutrient sensing. The mitochondrial and cytoskeletal abnormalities were validated in patient cells carrying mutations in NPC1, confirming their dysfunction in NPC disease.

scholarly journals Effects of curcumin nanoformulations on cellular function in Niemann-Pick disease type C astrocytes

2017 ◽  
Author(s):  
Emily Maguire ◽  
Luke J. Haslett ◽  
Joanne L. Welton ◽  
Helen Waller-Evans ◽  
Jule Goike ◽  
...  
Keyword(s):  
Clinical Evidence ◽  
Disease Type ◽  
Lipid Storage ◽  
Lysosomal Storage ◽  
Niemann Pick Disease ◽  
Type C ◽  
Niemann Pick ◽  
And Function ◽  
Pick Disease

AbstractNiemann-Pick disease type C1 (NPC disease) is a neurodegenerative multi-lipid lysosomal storage disease caused by mutations in the NPC1 gene presenting with reduced lysosomal Ca2+ signalling and inhibited late endosome-lysosome transport. Elevating cytosolic Ca2+ levels in NPC cells has been shown to reduce lysosomal lipid storage. Treating Npc1-/- mice with the Ca2+ modulator curcumin led to reduced lipid storage, improved life expectancy and function. These studies led to reported utilisation of curcumin supplements by NPC disease families despite there being no clinical evidence of benefit and a report indicating no benefit of nanoformulated curcumin in Npc1-/- mice. The aim of this study was to determine whether various commercially available curcumin nanoformulations were capable of reproducing the findings obtained with unformulated pharmaceutical grade curcumin. We compared seven curcumin nanoformulations in Npc1-/- mouse astrocytes. All the nanoformulations elevate cytosolic Ca2+ levels but only two lowered lysosomal lipid storage. Importantly, some caused elevations in NPC lysosomal storage and/or decreased cellular viability. Although this is an in vitro study, our findings suggest that care should be taken when contemplating the use of curcumin supplements for NPC disease.

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