CNS Drugs

, Volume 33, Issue 2, pp 125–142 | Cite as

Psychiatric and Cognitive Symptoms Associated with Niemann-Pick Type C Disease: Neurobiology and Management

  • Thomas RegoEmail author
  • Sarah Farrand
  • Anita M. Y. Goh
  • Dhamidhu Eratne
  • Wendy Kelso
  • Simone Mangelsdorf
  • Dennis Velakoulis
  • Mark Walterfang
Review Article


Niemann-Pick disease type C (NPC) is a lysosomal storage disorder that presents with a spectrum of clinical manifestations from infancy and childhood or in early or mid-adulthood. Progressive neurological symptoms including ataxia, dystonia and vertical gaze palsy are a hallmark of the disease, and psychiatric symptoms such as psychosis and mood disorders are common. These latter symptoms often present early in the course of NPC and thus these patients are often diagnosed with a major psychotic or affective disorder before neurological and cognitive signs present and the diagnosis is revised. The commonalities and characteristics of psychotic symptoms in both NPC and schizophrenia may share neuronal pathways and mechanisms and provide potential targets for research in both disorders. The neurobiology of NPC and its relationship to the pattern of neuropsychiatric and cognitive symptoms is described in this review. A number of neurobiological models are proposed as mechanisms by which NPC causes psychiatric and cognitive symptoms, informed from models proposed in schizophrenia and other metabolic disorders. There are a number of symptomatic and illness-modifying treatments for NPC currently available. The current evidence is discussed; focussing on two medications which have shown promise, miglustat and hydroxypropyl-β-cyclodextrin.


Compliance with Ethical Standards


Funding was received for medical illustrations for this article from an unrestricted educational grant provided by the Royal Melbourne Hospital.

Conflict of interest

Thomas Rego, Sarah Farrand, Anita M.Y. Goh, Dhamidhu Eratne, Wendy Kelso, Simone Mangelsdorf, Dennis Velakoulis and Mark Walterfang have no conflicts of interest to declare.


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© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Neuropsychiatry UnitThe Royal Melbourne HospitalMelbourneAustralia
  2. 2.Department of PsychiatryThe University of MelbourneMelbourneAustralia
  3. 3.National Ageing Research InstituteMelbourneAustralia
  4. 4.Melbourne Neuropsychiatry CentreUniversity of Melbourne and Melbourne HealthMelbourneAustralia
  5. 5.Movement Disorders ClinicKingston Centre, Monash HealthCheltenhamAustralia
  6. 6.Florey Institute of Neuroscience and Mental HealthMelbourneAustralia

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