Sleep disturbances and hypocretin deficiency in Niemann-Pick disease type C

Sleep. 2003 Jun 15;26(4):427-30. doi: 10.1093/sleep/26.4.427.


Design and patients: Subjects with Niemann-Pick disease, type C have been reported to display narcolepsylike symptoms, including cataplexy. In this study, 5 patients with juvenile Niemann-Pick disease were evaluted for sleep abnormalities using nocturnal polysomnography, clinical evaluation, and the Multiple Sleep Latency Test. HLA typing and cerebrospinal fluid hypocretin levels were also evaluated in 4 patients. Niemann-Pick disease diagnosis was confirmed in all cases biochemically and by the presence of foam cells in the bone marrow.

Results: Deterioration of intellectual function; the presence of pyramidal, dystonic and cerebellar features; and splenomegaly were observed in all cases. Cataplexy was reported in 1 patient. Nocturnal polysomnography revealed disrupted sleep in all patients. Total sleep time, sleep efficiency, rapid eye movement sleep, and delta sleep amounts were decreased when compared to age-matched controls. Altered sleep patterns included sudden increases in muscle tone during delta sleep, electroencephalographic sigma activity connected with rapid eye movements and muscle atonia, atypical K-complexes and spindle activity, and the presence of alpha-delta sleep. All Niemann-Pick disease cases exhibited fragmentary myoclonus. Shortened mean sleep latencies were observed in 3 patients during the Multiple Sleep Latency Test, but sleep-onset rapid eye movement periods were observed only in the case with cataplexy. This patient was HLA DQB1*0602 positive, while the other subjects were HLA negative. Cerebrospinal fluid hypocretin-1 levels were reduced in 2 patients (1 with cataplexy) while in the 2 other patients, the levels were at the lower range of the normal values. Hypocretin levels in the Niemann-Pick disease group (204.8 +/- 39.3 pg/mL) were significantly reduced when compared to controls (265.8 +/- 48.8 pg/mL).

Conclusions: The findings suggest that lysozomal storage abnormalities in Niemann-Pick disease patients may impact the hypothalamus and, more specifically, hypocretin-containing cells. These changes might be partially responsible for sleep abnormalities and cataplexy in patients with Niemann-Pick disease.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adolescent
  • Adult
  • Carrier Proteins / cerebrospinal fluid
  • Female
  • HLA-DQ Antigens / immunology
  • HLA-DQ beta-Chains
  • Humans
  • Hypothalamus / metabolism
  • Intracellular Signaling Peptides and Proteins*
  • Male
  • Neuropeptides / cerebrospinal fluid
  • Neuropeptides / deficiency*
  • Niemann-Pick Diseases / cerebrospinal fluid*
  • Niemann-Pick Diseases / complications*
  • Niemann-Pick Diseases / immunology
  • Orexins
  • Sleep Stages / physiology
  • Sleep Wake Disorders / etiology*
  • Wakefulness


  • Carrier Proteins
  • HCRT protein, human
  • HLA-DQ Antigens
  • HLA-DQ beta-Chains
  • HLA-DQB1 antigen
  • Intracellular Signaling Peptides and Proteins
  • Neuropeptides
  • Orexins