title: Niemann-Pick disease type C: cataplexy and hypocretin in cerebrospinal fluid.
abstract: Niemann-Pick disease type C (NPC) is an inherited lipid storage disorder, characterized by a defect in intracellular trafficking of exogenous cholesterol that leads to the lysosomal accumulation of unesterified cholesterol. We report a Japanese patient with NPC caused by a homozygous c.2974 G > T mutation of the NPC1 gene, which predicts a glycine (GGG) to tryptophan (TGG) change at codon 992 (designated as p.G992W). This is a well-known NPC1 gene mutation that causes a unique phenotype of NPC, which has been limited to a single Acadian ancestor in Nova Scotia, Canada. Our patient characteristically started presenting with cataplexy at the age of 9 years. Recent studies have shown reduced hypocretin-1 levels in the cerebrospinal fluid (CSF) of narcoleptic patients with cataplexy. In our patient, the level of hypocretin-1 was determined as moderately low, 174 pg/ml (normal, > 200 pg/ml). To date, CSF levels of hypocretin-1 have been determined by using an identical assay method in 7 cases of NPC, including our case. All of the NPC cases with cataplexy demonstrated low levels of CSF hypocretin-1, confirming the association of reduced CSF hypocretin-1 levels with cataplexy in NPC.
authors.affiliation: Department of Pediatrics, Akita University School of Medicine, Akita, Japan.
authors.forename: Katsuyuki
authors.initials: K
authors.lastname: Oyama
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Takahashi
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Shoji
authors.forename: Mika
authors.initials: M
authors.lastname: Oyamada
authors.forename: Atsuko
authors.initials: A
authors.lastname: Noguchi
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Tamura
authors.forename: Goro
authors.initials: G
authors.lastname: Takada
authors.forename: Takashi
authors.initials: T
authors.lastname: Kanbayashi
mesh_terms: D002352:Carrier Proteins / Q000235:genetics; D002385:Cataplexy / Q000209:etiology*; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D047908:Intracellular Signaling Peptides and Proteins / Q000134:cerebrospinal fluid* / Q000235:genetics; D008562:Membrane Glycoproteins / Q000235:genetics; D009479:Neuropeptides / Q000134:cerebrospinal fluid* / Q000235:genetics; D000077296:Niemann-Pick C1 Protein; D009542:Niemann-Pick Diseases / Q000134:cerebrospinal fluid* / Q000235:genetics; D000068797:Orexins; D017354:Point Mutation
chemical_list: D002352:Carrier Proteins; C000596229:HCRT protein, human; D047908:Intracellular Signaling Peptides and Proteins; D008562:Membrane Glycoproteins; C106881:NPC1 protein, human; D009479:Neuropeptides; D000077296:Niemann-Pick C1 Protein; D000068797:Orexins