Early detection of Niemann-pick disease type C with cataplexy and orexin levels: continuous observation with and without Miglustat

Orphanet Journal of Rare Diseases

T. Shimizu¹  T. Kawazoe²  T. Takahashi³  A. Noguchi³  K. Eto⁴  Y. Hamada⁵  K. Tsutsui⁶  A. Imanishi⁶  K. Mishima⁷  N. Sakai⁸  G. Han⁹  H. Kondo⁹  T. Kanbayashi⁹  T. Kumagai^1,10 

[1] Akita Mental Health and Welfare Center, Akita, Japan;Department of Neurology, National Center of Neurology and Psychiatry, Tokyo, Japan;Department of Pediatrics, Akita University Graduate School of Medicine, Akita, Japan;Department of Pediatrics, Tokyo Women’s Medical University, Tokyo, Japan;Department of Pediatrics, Toyonaka Municipal Hospital, Toyonaka, Japan;Department of Psychiatry, Akita University Graduate School of Medicine, Akita, Japan;Department of Psychiatry, Akita University Graduate School of Medicine, Akita, Japan;International Institute for Integrative Sleep Medicine (IIIS), University of Tsukuba, 305-8575, Tsukuba, Japan;Division of Health Sciences, Osaka University Graduate School of Medicine, Osaka, Japan;International Institute for Integrative Sleep Medicine (IIIS), University of Tsukuba, 305-8575, Tsukuba, Japan;National Center for Child Health and Development, Tokyo, Japan;

关键词: Niemann-pick type C (NPC);    Narcolepsy;    Cataplexy;    Orexin (hypocretin);    Miglustat;   

DOI  :  10.1186/s13023-020-01531-4

来源: Springer

【 摘 要 】

Study objectivesNiemann-Pick type C (NPC) is an autosomal recessive and congenital neurological disorder characterized by the accumulation of cholesterol and glycosphingolipids. Symptoms include hepatosplenomegaly, vertical supranuclear saccadic palsy, ataxia, dystonia, and dementia. Some cases frequently display narcolepsy-like symptoms, including cataplexy which was reported in 26% of all NPC patients and was more often recorded among late-infantile onset (50%) and juvenile onset (38%) patients. In this current study, we examined CSF orexin levels in the 10 patients of NPC with and without cataplexy, which supports previous findings.MethodsTen patients with NPC were included in the study (5 males and 5 females). NPC diagnosis was biochemically confirmed in all 10 patients, from which 8 patients with NPC1 gene were identified. We compared CSF orexin levels among NPC, narcoleptic and idiopathic hypersomnia patients.ResultsSix NPC patients with cataplexy had low or intermediate orexin levels. In 4 cases without cataplexy, their orexin levels were normal. In 5 cases with Miglustat treatment, their symptoms stabilized or improved. For cases without Miglustat treatment, their conditions worsened generally. The CSF orexin levels of NPC patients were significantly higher than those of patients with narcolepsy-cataplexy and lower than those of patients with idiopathic hypersomnia, which was considered as the control group with normal CSF orexin levels.DiscussionOur study indicates that orexin level measurements can be an early alert of potential NPC. Low or intermediate orexin levels could further decrease due to reduction in the neuronal function in the orexin system, accelerating the patients’ NPC pathophysiology. However with Miglustat treatment, the orexin levels stabilized or improved, along with other general symptoms. Although the circuitry is unclear, this supports that orexin system is indeed involved in narcolepsy-cataplexy in NPC patients.ConclusionThe NPC patients with cataplexy had low or intermediate orexin levels. In the cases without cataplexy, their orexin levels were normal. Our study suggests that orexin measurements can serve as an early alert for potential NPC; furthermore, they could be a marker of therapy monitoring during a treatment.

【 授权许可】

CC BY