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: Katsuyuki Oyama, Tsutomu Takahashi, Yutaka Shoji, Mika Oyamada, Atsuko Noguchi, Hiroaki Tamura, Goro Takada, Takashi Kanbayashi
• Journal: The Tohoku journal of experimental medicine (Tohoku J Exp Med) Vol. 209 Issue 3 Pg. 263-7 (Jul 2006) ISSN: 0040-8727 [Print] Japan
• PMID: 16778374 (Publication Type: Case Reports, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Carrier Proteins
• HCRT protein, human
• Intracellular Signaling Peptides and Proteins
• Membrane Glycoproteins
• NPC1 protein, human
• Neuropeptides
• Niemann-Pick C1 Protein
• Orexins

Topics

• Carrier Proteins (genetics)
• Cataplexy (etiology)
• Child
• Child, Preschool
• Female
• Humans
• Infant
• Infant, Newborn
• Intracellular Signaling Peptides and Proteins (cerebrospinal fluid, genetics)
• Membrane Glycoproteins (genetics)
• Neuropeptides (cerebrospinal fluid, genetics)
• Niemann-Pick C1 Protein
• Niemann-Pick Diseases (cerebrospinal fluid, genetics)
• Orexins
• Point Mutation