{"orpha":646,"name":"Niemann-Pick disease type C","type":"Disease","group":"Disorder","status":"active","flags":[],"synonyms":[],"definition":"A rare lysosomal lipid storage disease characterized by variable clinical signs, depending on the age of onset, such as prolonged unexplained neonatal jaundice or cholestasis, isolated unexplained splenomegaly, and progressive, often severe neurological symptoms such as cognitive decline, cerebellar ataxia, vertical supranuclear gaze palsy (VSPG), dysarthria, dysphagia, dystonia, seizures, gelastic cataplexy, and psychiatric disorders.","note":null,"url":"https://raremap.alftech.space/d/ORPHA-646/","orphanet_url":"https://www.orpha.net/en/disease/detail/646","names":{"fr":{"name":"Maladie de Niemann-Pick type C","definition":"Maladie lysosomale rare de surcharge lipidique caractérisée par des signes cliniques hétérogènes qui varient selon l'âge d'apparition, à savoir, un ictère ou une cholestase néonatale prolongée et inexpliquée, une splénomégalie isolée et inexpliquée, et des symptômes neurologiques progressifs, souvent sévères, tels qu'un déclin cognitif, une ataxie cérébelleuse, une paralysie supranucléaire verticale du regard (PSNV), une dysarthrie, une dysphagie, une dystonie, des crises convulsives, une cataplexie gélastique et des troubles psychiatriques."},"de":{"name":"Niemann-Pick-Krankheit Typ C","definition":"Eine seltene lysosomale Lipidspeicherkrankheit, die sich je nach Alter durch unterschiedliche klinische Symptome auszeichnet, wie z. B. anhaltende ungeklärte Neugeborenengelbsucht oder Cholestase, isolierte ungeklärte Splenomegalie und fortschreitende, oft schwere neurologische Symptome wie kognitiver Abbau, zerebelläre Ataxie, vertikale supranukleäre Blickparese (VSPG), Dysarthrie, Dysphagie, Dystonie, Krampfanfälle, gelastische Kataplexie und psychiatrische Störungen."},"es":{"name":"Enfermedad de Niemann-Pick tipo C","definition":"Es una enfermedad poco frecuente de depósito lisosomal de lípidos caracterizada por signos clínicos variables, en función de la edad de inicio, como ictericia neonatal prolongada e inexplicable o colestasis, esplenomegalia aislada e inexplicable, y síntomas neurológicos progresivos, a menudo graves, como declive cognitivo, ataxia cerebelosa, parálisis supranuclear de la mirada vertical (PSMV), disartria, disfagia, distonía, crisis, cataplexia gelástica y trastornos psiquiátricos."},"it":{"name":"Malattia di Niemann-Pick, tipo C","definition":"La malattia di Niemann-Pick tipo C (NPDC) è una lipidosi lisosomiale rara, caratterizzata, a seconda dell'età d'esordio, da segni clinici variabili, che comprendono l'ittero neonatale o la colestasi, prolungati e apparentemente inspiegabili, la splenomegalia isolata apparentemente inspiegabile, e sintomi neurologici progressivi, spesso gravi, come il deterioramento cognitivo, l'atassia cerebellare, l'oftalmoplegia verticale sopranucleare (VSPG), la disartria, la disfagia, la distonia, le crisi epilettiche, la cataplessia gelastica e le malattie psichiatriche."},"nl":{"name":"Ziekte van Niemann-Pick type C","definition":"Een zeldzame lysosomale vetstapelingsziekte, gekenmerkt door variabele klinische verschijnselen, afhankelijk van de aanvangsleeftijd, zoals langdurige onverklaarbare neonatale geelzucht of cholestase, geïsoleerde onverklaarbare splenomegalie, en progressieve, vaak ernstige neurologische symptomen zoals cognitieve aftakeling, cerebellaire ataxie, verticale supranucleaire blikparese, dysartrie, dysfagie, dystonie, insulten, gelastische kataplexie, en psychiatrische stoornissen."},"pt":{"name":"Doença de Niemann-Pick C","definition":"A doença de Niemann-Pick tipo C, distinta das formas tipos A e B, é uma lipidose lisossomal complexa que resulta em hepatosplenomegalia e envolvimento neurológico progressivo."},"pl":{"name":"Choroba Niemanna i Picka typu C"},"cs":{"name":"Niemannova-Pickova nemoc, typ C","synonyms":["Niemann-Pickova nemoc, typ C"]},"uk":{"name":"Хвороба Німана-Піка, тип С","definition":"A rare lysosomal lipid storage disease characterized by variable clinical signs, depending on the age of onset, such as prolonged unexplained neonatal jaundice or cholestasis, isolated unexplained splenomegaly, and progressive, often severe neurological symptoms such as cognitive decline, cerebellar ataxia, vertical supranuclear gaze palsy (VSPG), dysarthria, dysphagia, dystonia, seizures, gelastic cataplexy, and psychiatric disorders."},"zh":{"name":"Niemann-Pick病C型"},"tr":{"name":"Niemann-Pick hastalığı C tipi"}},"xrefs":[{"source":"OMIM","code":"257220","qualifier":"E","icd_relation":null,"validated":true},{"source":"OMIM","code":"607625","qualifier":"BTNT","icd_relation":null,"validated":true},{"source":"ICD-10","code":"E75.2","qualifier":"NTBT","icd_relation":"inclusion","validated":true},{"source":"ICD-11","code":"5C56.0Y","qualifier":"NTBT","icd_relation":"index","validated":true,"icd11_uri":"812702125"},{"source":"MONDO","code":"0018982","qualifier":"E","icd_relation":null,"validated":true},{"source":"MeSH","code":"D052556","qualifier":"E","icd_relation":null,"validated":true},{"source":"UMLS","code":"C0220756","qualifier":"E","icd_relation":null,"validated":true},{"source":"GARD","code":"7207","qualifier":"E","icd_relation":null,"validated":true}],"associations":[],"incoming_associations":[{"type":"Moved to","orpha":79289,"name":"Niemann-Pick disease type D","status":"inactive"}],"preferential_parent":{"orpha":68367,"name":"Rare inborn error of metabolism"},"parents":[{"orpha":98544,"name":"Cerebral lipidosis with dementia","classifications":[156,181]},{"orpha":183500,"name":"Genetic neurodegenerative disease","classifications":[156]},{"orpha":79204,"name":"Lipid storage disease","classifications":[150,156,233]},{"orpha":68385,"name":"Neurometabolic disease","classifications":[156,181]},{"orpha":717874,"name":"Rare inborn error of metabolism with inflammatory bowel disease","classifications":[152,156,233]},{"orpha":182070,"name":"Rare neurodegenerative disease","classifications":[181]},{"orpha":264968,"name":"Secondary interstitial lung disease in childhood and adulthood associated with a metabolic disease","classifications":[184,233]},{"orpha":371442,"name":"Sphingolipidosis with epilepsy","classifications":[156,181]},{"orpha":98687,"name":"Supranuclear eye movement disorder","classifications":[156,189]}],"children":[{"orpha":216986,"name":"Niemann-Pick disease type C, adult neurologic onset","type":"Clinical subtype"},{"orpha":216981,"name":"Niemann-Pick disease type C, juvenile neurologic onset","type":"Clinical subtype"},{"orpha":216978,"name":"Niemann-Pick disease type C, late infantile neurologic onset","type":"Clinical subtype"},{"orpha":216975,"name":"Niemann-Pick disease type C, severe early infantile neurologic onset","type":"Clinical subtype"},{"orpha":216972,"name":"Niemann-Pick disease type C, severe perinatal form","type":"Clinical subtype"}],"genes":[],"genes_via_subtypes":[{"symbol":"NPC1","name":"NPC intracellular cholesterol transporter 1","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"20301473[PMID]","hgnc":"7897","ensembl":"ENSG00000141458","omim":"607623","loci":["18q11.2"],"via":{"orpha":216972,"name":"Niemann-Pick disease type C, severe perinatal form"}},{"symbol":"NPC1","name":"NPC intracellular cholesterol transporter 1","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"20301473[PMID]","hgnc":"7897","ensembl":"ENSG00000141458","omim":"607623","loci":["18q11.2"],"via":{"orpha":216975,"name":"Niemann-Pick disease type C, severe early infantile neurologic onset"}},{"symbol":"NPC1","name":"NPC intracellular cholesterol transporter 1","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"20301473[PMID]","hgnc":"7897","ensembl":"ENSG00000141458","omim":"607623","loci":["18q11.2"],"via":{"orpha":216978,"name":"Niemann-Pick disease type C, late infantile neurologic onset"}},{"symbol":"NPC1","name":"NPC intracellular cholesterol transporter 1","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"20301473[PMID]","hgnc":"7897","ensembl":"ENSG00000141458","omim":"607623","loci":["18q11.2"],"via":{"orpha":216981,"name":"Niemann-Pick disease type C, juvenile neurologic onset"}},{"symbol":"NPC1","name":"NPC intracellular cholesterol transporter 1","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"20301473[PMID]","hgnc":"7897","ensembl":"ENSG00000141458","omim":"607623","loci":["18q11.2"],"via":{"orpha":216986,"name":"Niemann-Pick disease type C, adult neurologic onset"}},{"symbol":"NPC2","name":"NPC intracellular cholesterol transporter 2","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"20301473[PMID]","hgnc":"14537","ensembl":"ENSG00000119655","omim":"601015","loci":["14q24.3"],"via":{"orpha":216972,"name":"Niemann-Pick disease type C, severe perinatal form"}},{"symbol":"NPC2","name":"NPC intracellular cholesterol transporter 2","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"20301473[PMID]","hgnc":"14537","ensembl":"ENSG00000119655","omim":"601015","loci":["14q24.3"],"via":{"orpha":216975,"name":"Niemann-Pick disease type C, severe early infantile neurologic onset"}},{"symbol":"NPC2","name":"NPC intracellular cholesterol transporter 2","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"20301473[PMID]","hgnc":"14537","ensembl":"ENSG00000119655","omim":"601015","loci":["14q24.3"],"via":{"orpha":216978,"name":"Niemann-Pick disease type C, late infantile neurologic onset"}},{"symbol":"NPC2","name":"NPC intracellular cholesterol transporter 2","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) 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000","value":0.77,"area":"France","status":"Validated","source":"20525256[PMID]_12974729[PMID]_[EXPERT]"},{"type":"Prevalence at birth","qualification":"Value and class","class":"1-9 / 1 000 000","value":0.75,"area":"United Kingdom","status":"Not yet validated","source":"12974729[PMID]"},{"type":"Prevalence at birth","qualification":"Value and class","class":"1-9 / 1 000 000","value":0.75,"area":"Germany","status":"Not yet validated","source":"12974729[PMID]"},{"type":"Prevalence at birth","qualification":"Value and class","class":"1-9 / 1 000 000","value":0.35,"area":"Netherlands","status":"Validated","source":"10480370[PMID]"},{"type":"Prevalence at birth","qualification":"Value and class","class":"1-9 / 100 000","value":2.2,"area":"Portugal","status":"Validated","source":"14685153[PMID]"},{"type":"Prevalence at birth","qualification":"Value and class","class":"1-9 / 1 000 000","value":0.47,"area":"Australia","status":"Validated","source":"9918480[PMID]"},{"type":"Prevalence at birth","qualification":"Value and class","class":"1-9 / 1 000 000","value":0.91,"area":"Czech Republic","status":"Validated","source":"20490927[PMID]"},{"type":"Prevalence at birth","qualification":"Value and class","class":"1-9 / 1 000 000","value":0.48,"area":"Sweden","status":"Validated","source":"25274184[PMID]"}],"phenotypes":{"validation_status":"y","online":"y","validation_date":"2020-04-06","source":"20301473[PMID]_30285904[PMID]_30205942[PMID]_20525256[PMID]_23760316[PMID]_12873889[PMID]","terms":[{"hpo":"HP:0001392","label":"Abnormality of the liver","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0000708","label":"Atypical behavior","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0002015","label":"Dysphagia","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0001288","label":"Gait disturbance","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0002240","label":"Hepatomegaly","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0000952","label":"Jaundice","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0003349","label":"Low cholesterol esterification rate","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0001268","label":"Mental deterioration","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0002344","label":"Progressive neurologic deterioration","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0000511","label":"Vertical supranuclear gaze palsy","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0011446","label":"Abnormality of higher mental function","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0100022","label":"Abnormality of movement","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002167","label":"Abnormality of speech or vocalization","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0010318","label":"Aplasia/Hypoplasia of the abdominal wall musculature","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001251","label":"Ataxia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002530","label":"Axial dystonia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0004333","label":"Bone-marrow foam cells","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0100543","label":"Cognitive impairment","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001260","label":"Dysarthria","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001618","label":"Dysphonia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001332","label":"Dystonia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0011968","label":"Feeding difficulties","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0003651","label":"Foam cells","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000365","label":"Hearing impairment","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002451","label":"Limb dystonia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0007240","label":"Progressive gait ataxia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001250","label":"Seizure","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001744","label":"Splenomegaly","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0011400","label":"Abnormal CNS myelination","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0007256","label":"Abnormal pyramidal sign","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0012433","label":"Abnormal social behavior","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000718","label":"Aggressive behavior","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000741","label":"Apathy","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0008765","label":"Auditory hallucinations","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002524","label":"Cataplexy","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0006855","label":"Cerebellar vermis atrophy","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002059","label":"Cerebral atrophy","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002072","label":"Chorea","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002312","label":"Clumsiness","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000722","label":"Compulsive behaviors","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000750","label":"Delayed speech and language development","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000726","label":"Dementia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000716","label":"Depression","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002376","label":"Developmental regression","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000734","label":"Disinhibition","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0007359","label":"Focal-onset seizure","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002359","label":"Frequent falls","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0011471","label":"Gastrostomy tube feeding in infancy","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002197","label":"Generalized-onset seizure","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001263","label":"Global developmental delay","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001433","label":"Hepatosplenomegaly","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002079","label":"Hypoplasia of the corpus callosum","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001252","label":"Hypotonia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001249","label":"Intellectual disability","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002080","label":"Intention tremor","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002415","label":"Leukodystrophy","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000744","label":"Low frustration tolerance","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002061","label":"Lower limb spasticity","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0011369","label":"Mongolian blue spot","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001336","label":"Myoclonus","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0030050","label":"Narcolepsy","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000709","label":"Psychosis","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0100753","label":"Schizophrenia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002360","label":"Sleep abnormality","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001328","label":"Specific learning disability","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0011098","label":"Speech apraxia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001337","label":"Tremor","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002493","label":"Upper motor neuron dysfunction","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002367","label":"Visual hallucinations","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002088","label":"Abnormal lung morphology","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0001541","label":"Ascites","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0011951","label":"Aspiration pneumonia","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0007302","label":"Bipolar affective disorder","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0007108","label":"Demyelinating peripheral neuropathy","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0001791","label":"Fetal ascites","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0006913","label":"Frontal cortical atrophy","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0001399","label":"Hepatic failure","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0001789","label":"Hydrops fetalis","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0002113","label":"Pulmonary infiltrates","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0002878","label":"Respiratory failure","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0002093","label":"Respiratory insufficiency","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0002133","label":"Status epilepticus","frequency":"Very rare (<4-1%)","criteria":null}]}}