3,802 results match your criteria Niemann-Pick Disease


Inborn Errors of Metabolism Associated With Autism Spectrum Disorders: Approaches to Intervention.

Front Neurosci 2021 28;15:673600. Epub 2021 May 28.

Department of Paediatrics, University Hospital Center Zagreb and University of Zagreb School of Medicine, Zagreb, Croatia.

Increasing evidence suggests that the autism spectrum disorder (ASD) may be associated with inborn errors of metabolism, such as disorders of amino acid metabolism and transport [phenylketonuria, homocystinuria, S-adenosylhomocysteine hydrolase deficiency, branched-chain α-keto acid dehydrogenase kinase deficiency, urea cycle disorders (UCD), Hartnup disease], organic acidurias (propionic aciduria, L-2 hydroxyglutaric aciduria), cholesterol biosynthesis defects (Smith-Lemli-Opitz syndrome), mitochondrial disorders (mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes-MELAS syndrome), neurotransmitter disorders (succinic semialdehyde dehydrogenase deficiency), disorders of purine metabolism [adenylosuccinate lyase (ADSL) deficiency, Lesch-Nyhan syndrome], cerebral creatine deficiency syndromes (CCDSs), disorders of folate transport and metabolism (cerebral folate deficiency, methylenetetrahydrofolate reductase deficiency), lysosomal storage disorders [Sanfilippo syndrome, neuronal ceroid lipofuscinoses (NCL), Niemann-Pick disease type C], cerebrotendinous xanthomatosis (CTX), disorders of copper metabolism (Wilson disease), disorders of haem biosynthesis [acute intermittent porphyria (AIP)] and brain iron accumulation diseases. In this review, we briefly describe etiology, clinical presentation, and therapeutic principles, if they exist, for these conditions. Additionally, we suggest the primary and elective laboratory work-up for their successful early diagnosis. Read More

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A phase 1/2 open label nonrandomized clinical trial of intravenous 2-hydroxypropyl-β-cyclodextrin for acute liver disease in infants with Niemann-Pick C1.

Mol Genet Metab Rep 2021 Sep 26;28:100772. Epub 2021 May 26.

Washington University in St. Louis School of Medicine, St. Louis, MO, United States of America.

Introduction: Niemann-Pick C (NPC) is an autosomal recessive disease due to defective NPC1 or NPC2 proteins resulting in -lysosomal storage of unesterified cholesterol in the central nervous system and liver. Acute liver disease in the newborn period may be self-limited or fatal. 2-hydroxypropyl-β-cyclodextrin (2HPBCD) is a cholesterol-binding agent that reduces lysosomal cholesterol storage. Read More

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September 2021

Spatiotemporal Developmental Upregulation of Prestin Correlates With the Severity and Location of Cyclodextrin-Induced Outer Hair Cell Loss and Hearing Loss.

Front Cell Dev Biol 2021 24;9:643709. Epub 2021 May 24.

Center for Hearing and Deafness, University at Buffalo, Buffalo, NY, United States.

2-Hyroxypropyl-beta-cyclodextrin (HPβCD) is being used to treat Niemann-Pick C1, a fatal neurodegenerative disease caused by abnormal cholesterol metabolism. HPβCD slows disease progression, but unfortunately causes severe, rapid onset hearing loss by destroying the outer hair cells (OHC). HPβCD-induced damage is believed to be related to the expression of prestin in OHCs. Read More

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Naturally occurring anti-Kp in an infant with recurrent bacterial infection: A case report and review of the literature.

Vox Sang 2021 Jun 8. Epub 2021 Jun 8.

Department of Immunohematology & Blood Transfusion, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, Karnataka, India.

Naturally occurring anti-Kp antibody is extremely rare and was first reported in 1957, named after the first producer 'Penney'. However, the subsequent anti-Kp reports presented were all anti-Kp due to isoimmunization. Individuals with severe bacterial infections particularly Gram-negative bacteria are known to be capable of producing cross-reactive antibodies against Kell blood group system. Read More

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[Diffuse parenchymal lung diseases in Niemann-Pick disease type C2].

Zhonghua Er Ke Za Zhi 2021 Jun;59(6):519-521

Department of Pulmonology, the Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou 310052, China.

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A cross-sectional, prospective ocular motor study in 72 patients with Niemann-Pick disease type C.

Eur J Neurol 2021 Jun 7. Epub 2021 Jun 7.

German Center for Vertigo and Balance Disorders and Department of Neurology, University Hospital Munich, Campus Grosshadern, Ludwig-Maximilians-University Munich, Germany.

Objective: To characterize ocular motor function in patients with Niemann-Pick type C (NPC).

Methods: In a multicontinental, cross-sectional study we characterized ocular-motor function in 72 patients from twelve countries by video-oculography. Interlinking with disease severity, we also searched for ocular motor biomarkers. Read More

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Prevalence of patients with lysosomal storage disorders and peroxisomal disorders: A nationwide survey in Japan.

Mol Genet Metab 2021 May 12. Epub 2021 May 12.

Advanced Clinical Research Center, Southern Tohoku Research Center for Neuroscience, Kanagawa, Japan.

Introduction: Lysosomal storage disorders and peroxisomal disorders are rare diseases caused by the accumulation of substrates of the metabolic pathway within lysosomes and peroxisomes, respectively. Owing to the rarity of these diseases, the prevalence of lysosomal storage disorders and peroxisomal disorders in Japan is unknown. Therefore, we conducted a nationwide survey to estimate the number of patients with lysosomal storage disorders and peroxisomal disorders in Japan. Read More

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Vertical saccadic palsy and foveal retinal thinning in Niemann-Pick disease type C.

PLoS One 2021 4;16(6):e0252825. Epub 2021 Jun 4.

Department of Ophthalmology, University Medical Center Mainz, Mainz, Germany.

Introduction: Niemann-Pick type C (NPC) is a lysosomal storage disease that is progressive and life-limiting, with an estimated incidence of 1:120,000 live births. In addition to systemic manifestation with (hepato-)splenomegaly, there are a number of neurological manifestations (ataxia, dysarthria, dementia, cataplexy, epileptic seizures, and psychiatric disorders). Characteristic is vertical supranuclear gaze palsy, which is often overlooked. Read More

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Lipid-mediated impairment of axonal lysosome transport contributing to autophagic stress.

Autophagy 2021 Jun 4. Epub 2021 Jun 4.

Synaptic Function Section, The Porter Neuroscience Research Center, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Room 2B-215, 35 Convent Drive, Bethesda, Maryland 20892-3706, USA.

Efficient degradation of autophagic vacuoles (AVs) generated at axon terminals by mature lysosomes enriched in the cell body represents an exceptional challenge that neurons face in maintaining cellular homeostasis. Here, we discuss our recent findings revealing a lipid-mediated impairment of lysosome transport to distal axons contributing to axonal AV accumulation in the neurodegenerative lysosomal storage disorder Niemann-Pick disease type C (NPC). Using transmission electron microscopy, we observed a striking buildup of endocytic and autophagic organelles in NPC dystrophic axons, indicating defects in the clearance of organelles destined for lysosomal degradation. Read More

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Engineered Human Monoclonal scFv to Receptor Binding Domain of .

Vaccines (Basel) 2021 May 4;9(5). Epub 2021 May 4.

Center of Research Excellence on Therapeutic Proteins and Antibody Engineering, Department of Parasitology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand.

(1) Background: (EBOV) poses as a significant threat for human health by frequently causing epidemics of the highly contagious Ebola virus disease (EVD). EBOV glycoprotein (GP), as a sole surface glycoprotein, needs to be cleaved in endosomes to fully expose a receptor-binding domain (RBD) containing a receptor-binding site (RBS) for receptor binding and genome entry into cytoplasm for replication. RBDs are highly conserved among EBOV species, so they are an attractive target for broadly effective anti-EBOV drug development. Read More

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Three-Dimensional Imaging of Whole-Body Zebrafish Revealed Lipid Disorders Associated with Niemann-Pick Disease Type C1.

Anal Chem 2021 Jun 1;93(23):8178-8187. Epub 2021 Jun 1.

Guangzhou Key Laboratory of Environmental Catalysis and Pollution Control, Guangdong Key Laboratory of Environmental Catalysis and Health Risk Control, School of Environmental Science and Engineering, Institute of Environmental Health and Pollution Control, Guangdong University of Technology, Guangzhou 510006, China.

Imaging of lipids of whole-body specimens in two-dimensional (2D) analysis provides a global picture of the lipid changes in lipid-disturbed diseases, enabling a better understanding of lipid functions and lipid-modulation processes in different organs. However, 2D imaging of a single cross section can hardly characterize the whole-body lipid alterations. In this work, a three-dimensional matrix-assisted laser desorption/ionization mass spectrometry imaging (3D MALDI-MSI) approach was developed for analysis of whole-body zebrafish, for the first time, and applied to identify altered lipids and map their spatial distributions by using a zebrafish model of Niemann-Pick disease type C1 (NPC1), a neurovisceral lipid storage disorder causing both neurodegenerative disorder and visceral organ damage. Read More

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TDP-43 proteinopathy occurs independently of autophagic substrate accumulation and underlies nuclear defects in Niemann-Pick C disease.

Neuropathol Appl Neurobiol 2021 May 28. Epub 2021 May 28.

Department of Pathology, University of Michigan Medical School, Ann Arbor, MI, USA.

Aims: Neuronal cytoplasmic inclusions of TAR-DNA binding protein of 43 kDa (TDP-43) are a pathological hallmark of diverse neurodegenerative disorders, yet the processes that mediate their formation and their functional significance remain incompletely understood. Both dysfunction in autophagy and neuroinflammation have been linked to TDP-43 mislocalisation. Here, we investigate TDP-43 proteinopathy in Niemann-Pick type C disease (NPC), an autosomal recessive lysosomal storage disease (LSD) distinguished by the accumulation of unesterified cholesterol within late endosomes and lysosomes. Read More

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Platycodin D, a natural component of Platycodon grandiflorum, prevents both lysosome- and TMPRSS2-driven SARS-CoV-2 infection by hindering membrane fusion.

Exp Mol Med 2021 05 25;53(5):956-972. Epub 2021 May 25.

Center for Cognition and Sociality, Cognitive Glioscience Group, Institute for Basic Science, Daejeon, 34126, Republic of Korea.

An ongoing pandemic of coronavirus disease 2019 (COVID-19) is now the greatest threat to global public health. Herbal medicines and their derived natural products have drawn much attention in the treatment of COVID-19, but the detailed mechanisms by which natural products inhibit SARS-CoV-2 have not been elucidated. Here, we show that platycodin D (PD), a triterpenoid saponin abundant in Platycodon grandiflorum (PG), a dietary and medicinal herb commonly used in East Asia, effectively blocks the two main SARS-CoV-2 infection routes via lysosome- and transmembrane protease serine 2 (TMPRSS2)-driven entry. Read More

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Enrichment of NPC1-deficient cells with the lipid LBPA stimulates autophagy, improves lysosomal function, and reduces cholesterol storage.

J Biol Chem 2021 May 20:100813. Epub 2021 May 20.

Department of Nutritional Sciences, Rutgers University, New Brunswick, NJ 08901, USA; Rutgers Center for Lipid Research, Rutgers University, New Brunswick, NJ 08901 USA. Electronic address:

Niemann-Pick C (NPC) is an autosomal recessive disorder characterized by mutations in the NPC1 or NPC2 genes encoding endo-lysosomal lipid transport proteins, leading to cholesterol accumulation and autophagy dysfunction. We have previously shown that enrichment of NPC1-deficient cells with the anionic lipid lysobisphosphatidic acid (LBPA; also called bis(monoacylglycerol)phosphate, BMP) via treatment with its precursor phosphatidylglycerol (PG) results in a dramatic decrease in cholesterol storage. However, the mechanisms underlying this reduction are unknown. Read More

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Neuropsychological assessment in Niemann-Pick disease type C: a systematic review.

Neurol Sci 2021 May 22. Epub 2021 May 22.

IRCCS Centro Neurolesi "Bonino-Pulejo", S.S. 113, Contrada Casazza, 98124, Messina, Italy.

Background: The neuropsychological profile of Niemann-Pick type C (NP-C) patients is characterized by an early deterioration in executive functions and attention. There are few studies on cognitive impairment and on neuropsychological assessment of NP-C disease. The purpose of this review is to analyze the studies on a psychological assessment for NP-C patients. Read More

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NPC1 regulates the distribution of phosphatidylinositol 4-kinases at Golgi and lysosomal membranes.

EMBO J 2021 May 21:e105990. Epub 2021 May 21.

Department of Physiology and Membrane Biology, University of California, Davis, CA, USA.

Cholesterol and phosphoinositides (PI) are two critically important lipids that are found in cellular membranes and dysregulated in many disorders. Therefore, uncovering molecular pathways connecting these essential lipids may offer new therapeutic insights. We report that loss of function of lysosomal Niemann-Pick Type C1 (NPC1) cholesterol transporter, which leads to neurodegenerative NPC disease, initiates a signaling cascade that alters the cholesterol/phosphatidylinositol 4-phosphate (PtdIns4P) countertransport cycle between Golgi-endoplasmic reticulum (ER), as well as lysosome-ER membrane contact sites (MCS). Read More

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Lysosomes to the rescue: Anterograde axonal lysosome transport and neuronal proteostasis.

Dev Cell 2021 May;56(10):1361-1362

Department of Cell Biology, University of Virginia, 1340 Jefferson Park Avenue, Pinn Hall Room 3226, Charlottesville, VA 22908, USA. Electronic address:

Niemann-Pick is a lysosomal storage disease caused by loss of the lysosomal cholesterol exporter NPC1 and leads to axon degeneration. Roney et al. report that immature autophagosomes accumulate in axons because cholesterol-laden lysosomes in the soma are not transported to the axon for autophagosome fusion and maturation because they aberrantly sequester non-functioning kinesin-1. Read More

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Identification and Classification of Rare Variants in NPC1 and NPC2 in Quebec.

Sci Rep 2021 May 14;11(1):10344. Epub 2021 May 14.

Départment de Neurosciences, Faculté de Médecine, Université de Montréal, CRCHUM - 900, rue Saint-Denis, Pavillon R, Montréal, QC, H2X 0A9, Canada.

Niemann-Pick disease type C (NPC) is a treatable autosomal recessive neurodegenerative condition which leads to a variety of progressive manifestations. Despite most cases being diagnosed at a young age, disease prevalence may be underestimated, especially in adults, and interpretation of NPC1 and NPC2 variants can be difficult. This study aims to identify potential pathogenic variants in a large cohort of healthy individuals and classify their risk of pathogenicity to assist with future interpretation of variants. Read More

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-Deficient Zebrafish Reproduce Neurological and Inflammatory Symptoms of Niemann-Pick Type C Disease.

Front Cell Neurosci 2021 27;15:647860. Epub 2021 Apr 27.

Laboratory of Neurodegeneration, International Institute of Molecular and Cell Biology in Warsaw, Warsaw, Poland.

Niemann-Pick type C (NPC) disease is an autosomal recessive lysosomal storage disease that is caused by a mutation of the or gene, in which un-esterified cholesterol and sphingolipids accumulate mainly in the liver, spleen, and brain. Abnormal lysosomal storage leads to cell damage, neurological problems, and premature death. The time of onset and severity of symptoms of NPC disease are highly variable. Read More

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Gastrodiae rhizoma attenuates brain aging via promoting neuritogenesis and neurodifferentiation.

Phytomedicine 2021 Jul 18;87:153576. Epub 2021 Apr 18.

Department of Chinese Pharmaceutical Sciences and Chinese Medicine Resources, China Medical University, Taichung 40402, Taiwan; Department of Pharmacy, National Taiwan University, Taipei 10050, Taiwan. Electronic address:

Background: Gastrodiae Rhizoma (Tianma), the dried tuber of Gastrodia elata Bl. (Orchidaceae), is listed as a top-grade herbal medicine in Shen-nong Ben-ts'ao Jing and has been used for treating headaches, dizziness, vertigo and convulsion. It has a neuroprotective effect and extends the lifespan in mouse models of Huntington's disease and Niemann-Pick type C disease. Read More

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Prospective study of the natural history of chronic acid sphingomyelinase deficiency in children and adults: eleven years of observation.

Orphanet J Rare Dis 2021 May 10;16(1):212. Epub 2021 May 10.

Sanofi Genzyme, Cambridge, MA, USA.

Background: Acid sphingomyelinase deficiency (ASMD) (also known as Niemann-Pick disease types A and B) is a rare and debilitating lysosomal storage disorder. This prospective, multi-center, multinational longitudinal study aimed to characterize the clinical features of chronic forms of ASMD and disease burden over time in children and adults.

Results: Fifty-nine patients (31 males/28 females) ranging in age from 7 to 64 years with chronic ASMD types A/B and B and at least two disease symptoms participated from 5 countries. Read More

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Bilateral Cystic Bronchiectasis as Novel Phenotype of Niemann-Pick Disease Type B Successfully Treated With Double Lung Transplantation.

Chest 2021 May;159(5):e293-e297

Department of Internal Medicine and Therapeutics, Division of Respiratory Diseases, University of Pavia and IRCCS Policlinico San Matteo Foundation, Pavia, Italy.

Niemann-Pick Disease type B (NPDB) is a rare autosomal recessive disease belonging to the family of lysosomal storage disorders. NPDB is caused by mutations of sphingomyelin phosphodiesterase 1 gene (SMPD1) and is characterized by hepatosplenomegaly, interstitial lung disease, recurrent pulmonary infections, and neurologic disorders. Bronchiectasis are atypical. Read More

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Complications associated with intrathecal drug delivery in a paediatric patient with Niemann-Pick type C.

BMJ Case Rep 2021 May 7;14(5). Epub 2021 May 7.

Neurosurgery, Great Ormond Street Hospital for Children, London, UK.

We report on a male subject with a diagnosis of Niemann-Pick type C (NPC). He received an experimental medicinal product intrathecally initially via lumbar puncture (LP) and eventually via intrathecal drug delivery device. Shortly after implantation, the device catheter migrated outside of the intrathecal space and coiled subcutaneously. Read More

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A randomised evaluation of low-dose cytosine arabinoside (ara-C) plus tosedostat versus low-dose ara-C in older patients with acute myeloid leukaemia: results of the LI-1 trial.

Br J Haematol 2021 May 7. Epub 2021 May 7.

Department of Haematology, Nottingham University Hospitals, Nottingham, UK.

Older patients with acute myeloid leukaemia (AML) account for nearly half of those with the disease. Because they are perceived to be unfit for, unwilling to receive, or unlikely to benefit from conventional chemotherapy they represent an important unmet need. Tosedostat is a selective oral aminopeptidase inhibitor, which in phase I/II trials showed acceptable toxicity and encouraging efficacy. Read More

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Additive effect of frequent polymorphism and rare synonymous variant alters splicing in twin patients with Niemann-Pick disease type C.

Eur J Hum Genet 2021 May 6. Epub 2021 May 6.

Research Centre for Medical Genetics, Moscow, Russia.

Niemann-Pick disease type C (NP-C) (OMIM#257220) is a rare lysosomal storage disorder caused by pathogenic variants in either the NPC1 or NPC2 genes. It manifests with a wide spectrum of clinical symptoms and variable age of onset. We studied the impact of the frequent polymorphic variant c. Read More

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Repurposing Vorinostat for the Treatment of Disorders Affecting Brain.

Neuromolecular Med 2021 May 4. Epub 2021 May 4.

Applied Biology Division, CSIR- Indian Institute of Chemical Technology, Tarnaka, Uppal Road, Hyderabad, 500007, Telangana, India.

Based on the findings in recent years, we summarize the therapeutic potential of vorinostat (VOR), the first approved histone deacetylase (HDAC) inhibitor, in disorders of brain, and strategies to improve drug efficacy and reduce side effects. Scientific evidences provide a strong case for the therapeutic utility of VOR in various disorders affecting brain, including stroke, Alzheimer's disease, frontotemporal dementia, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, spinal muscular atrophy, X-linked adrenoleukodystrophy, epilepsy, Niemann-Pick type C disease, and neuropsychiatric disorders. Further elucidation of the neuroprotective and neurorestorative properties of VOR using proper clinical study designs could provide momentum towards its clinical application. Read More

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A Niemann-pick C1 disease child with BCG-itis: a case report and analysis.

BMC Pediatr 2021 05 4;21(1):218. Epub 2021 May 4.

Shanghai Public Health Clinical Center, Fudan University, Shanghai, China.

Background: Niemann-Pick C disease is a rare autosomal recessive lysosomal lipid storage disorder. Some primary immunodeficiency diseases patients developed regional disease or disseminated disease after vaccinating BCG. It is unclear whether NPC gene deficiency is associated with Mycobacteria infection. Read More

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Inhibitors of Protein Glycosylation Are Active against the Coronavirus Severe Acute Respiratory Syndrome Coronavirus SARS-CoV-2.

Viruses 2021 04 30;13(5). Epub 2021 Apr 30.

Laboratory of Molecular Virology, International Centre for Genetic Engineering and Biotechnology (ICGEB) Padriciano, 99-34149 Trieste, Italy.

Repurposing clinically available drugs to treat the new coronavirus disease 2019 (COVID-19) is an urgent need in the course of the Severe Acute Respiratory Syndrome coronavirus (SARS-CoV-2) pandemic, as very few treatment options are available. The iminosugar Miglustat is a well-characterized drug for the treatment of rare genetic lysosome storage diseases, such as Gaucher and Niemann-Pick type C, and has also been described to be active against a variety of enveloped viruses. The activity of Miglustat is here demonstrated in the micromolar range for SARS-CoV-2 in vitro. Read More

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Possible genotype-phenotype correlations in Niemann-Pick type C patients and miglustat treatment.

Ideggyogy Sz 2021 Mar;74(3-4):139-144

Division of Pediatric Metabolism, University of Health Sciences, Kanuni Sultan Süleyman Training and Research Hospital, İstanbul, Turkey.

Background And Purpose: Niemann-Pick type C is a rare lysosomal storage disease caused by impaired intracellular cholesterol transport. The autosomal recessive disease is caused by mutations in NPC1 or NPC2 genes.

Methods: Clinical-laboratory features, genotype-phenotype correlation and miglustat treatment response of our patients diagnosed with early infantile Niemann-Pick type C were evaluated. Read More

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