Niemann–Pick disease type C

Page most recently updated 7 September 2026

This page focuses on the reported psychiatric associations, which may be the initial presenting manifestation, and on other clinical features that may assist the psychiatrist or primary care physician in identifying the underlying diagnosis, considered through the lenses of the diagnostic lenses framework.

Niemann–Pick disease type C is a genetic neurometabolic disorder of intracellular lipid trafficking that can affect neurodevelopment, mental health, movement, cognition, and multiple organ systems. It typically occurs as an inherited autosomal recessive genetic condition. De novo variants are rarer. Affected individuals may have no previously recognized family history because their parents are typically unaffected carriers. Vertical supranuclear gaze palsy and cataplexy are particularly useful neurologic clues.

It can present with psychiatric features such as psychosis, depression, anxiety, cognitive or behavioural change, irritability, and other mood or behavioural abnormalities. Psychiatric manifestations may become apparent or clinically significant during adolescence or adulthood and may precede the characteristic neurologic manifestations. Psychosis may be prominent, including in individuals initially diagnosed with a primary schizophrenia-spectrum or mood disorder.

Other characteristic features include vertical supranuclear gaze palsy, cerebellar ataxia, dysarthria, dysphagia, dystonia, parkinsonism, seizures, cognitive decline, and progressive impairment of coordination and gait. Gelastic cataplexy, often presenting as sudden loss of muscle tone triggered by laughter or other positive emotions, is particularly characteristic. Hepatosplenomegaly or isolated splenomegaly may occur, particularly in childhood-onset disease, although visceral manifestations may be subtle or absent in later-onset disease.

From a multisystemic lens perspective, clinical features in other body systems include (but are not limited to):

  • Hepatobiliary: hepatosplenomegaly, neonatal cholestasis, and other hepatic manifestations may occur, particularly in early-onset disease.

  • Hematologic: cytopenias, particularly thrombocytopenia, may occur, especially in association with splenomegaly.

Early diagnosis is important because a psychiatric presentation can precede the characteristic neurologic manifestations of this treatable neurometabolic disorder. It is also important to identify potentially reversible or manageable contributors to psychiatric and cognitive symptoms, recognize progressive neurologic and swallowing complications, initiate disease-specific treatment and supportive care, avoid diagnostic delay in individuals presenting with atypical or treatment-resistant psychiatric illness, and enable appropriate genetic counselling and screening of at-risk relatives.

Selected references and further reading — Multisystemic lens

Cardinal RN, Bullmore ET. The diagnosis of psychosis. Cambridge: Cambridge University Press; 2011.

Sachdev PS, Keshavan MS, editors. Secondary schizophrenia. Cambridge: Cambridge University Press; 2010.

Levenson JL, editor. The American Psychiatric Association Publishing textbook of psychosomatic medicine and consultation-liaison psychiatry. 3rd ed. Washington (DC): American Psychiatric Association Publishing; 2019.

Stern TA, Beach SR, Smith FA, Freudenreich O, Vranceau AM, Fava M, editors. Massachusetts General Hospital handbook of general hospital psychiatry. 8th ed. Philadelphia: Elsevier; 2025.

Arciniegas DB, Yudofsky SC, Hales RE, editors. The American Psychiatric Association Publishing textbook of neuropsychiatry and clinical neurosciences. 6th ed. Washington (DC): American Psychiatric Association Publishing; 2018.

Agrawal N, Faruqui R, Bodani M, editors. Oxford textbook of neuropsychiatry. Oxford: Oxford University Press; 2020.

Boland R, Verduin M, editors. Kaplan and Sadock's comprehensive textbook of psychiatry. 11th ed. Philadelphia: Wolters Kluwer; 2024.

Loscalzo J, Fauci AS, Kasper DL, Hauser SL, Longo DL, Jameson JL, editors. Harrison's principles of internal medicine. 22nd ed. New York: McGraw Hill; 2025.