Niemann-Pick Disease Type C – Example of an Inborn Error of Metabolism Producing Psychiatric Manifestations

Olivier Bonnot
European Psychiatric Review, 2011;4(2):84-88
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Abstract

Organic schizophrenia, or schizophrenia-like syndrome, is an important concern in psychiatry. Its incidence is unknown due to difficulties in symptom recognition and changing symptoms over time. It is important to be aware that these symptoms could be the single manifestation of a specific organic disease, such as Niemann-Pick disease type C (NPC). NPC is a pan-ethnic, autosomal recessive neurodegenerative disease that has been reported to cause schizophrenic symptoms in adult and adolescent patients. Symptoms of early-onset schizophrenia occurring in young patients often lead to a misdiagnosis and up to a two to 10 year delay before NPC is confirmed. It is not practical to investigate all patients with schizophrenia for an organic aetiology of their disease, but it can be useful to monitor atypical signs of psychosis or minor physical signs such as vertical supranuclear ophthalmoplegia. Until recently, therapy for NPC was limited to supportive measures. However, a recently licensed medication is now available to treat the psychiatric manifestations of NPC. This review article focuses on those manifestations, and describes a clinical tool developed to help clinicians identify which ones should trigger efforts to detect organic disease.
Keywords
Lipid storage disorder, miglustat, neurological, neuropsychiatric disorder, Niemann-Pick disease type C, organic schizophrenia
Disclosure The author has no conflicts of interest to declare.
Received: February 11, 2011 Accepted June 16, 2011
Correspondence: Olivier Bonnot, Centre Référent Maladie Rare à Expression Psychiatrique, Service de Psychiatrie de l’Enfant et de l’Adolescent, Groupe Hospitalier Pitié Salpêtrière, Assistance Publique-Hôpitaux de Paris, 47-83 boulevard de l’Hôpital, 75013 Paris, France. E: olivier.bonnot@psl.aphp.fr

Organic conditions associated with psychiatric symptoms or syndromes are universally studied by physicians during their training at medical school, yet are poorly diagnosed and treated in clinical practice. The association of hypothyroidism with depression, of Cushing’s disease with maniac episodes or of Wilson’s disease with schizophrenia-like behaviour is well known and documented, but, sadly, many such conditions go undetected and untreated for extended periods of time. This situation needs to be improved, particularly when somatic treatments that can alleviate some, or even all, of the psychiatric symptoms arising from such organic conditions are available. In this article we will focus on the schizophrenia-like symptoms associated with Niemann-Pick disease type C (NPC), which is an example of a treatable condition resulting from an inborn error of metabolism (IEM).

Organic schizophrenia, or schizophrenia-like syndrome, is an important concern in psychiatry1 and various medical conditions and substances may be associated with it.2 One major issue is that its incidence is unknown as a result of two important factors described below.

  • The extensive and exhaustive monitoring of organic schizophrenia is impossible due to difficulties in symptom recognition and the changing nature of symptoms over time. A study of 268 patients with a first episode of schizophrenia – one of the largest of its kind – found that less than 6 % had organic disease.3 Indirect evidence of organic disease associated with catatonia or early-onset schizophrenia shows no rare organic association in these populations.4,5
  • The worldwide prevalence of schizophrenia is estimated to be approximately 0.8 %, but its worldwide incidence is much higher and variable (median 15.2/100,000 population [10–90 % quantile: 7.7–43.0/100,000]) due to the chronic course of the disease.6–8 Its association with rare organic diseases may therefore be coincidental, despite the conclusion of a large review in 1983 that it exceeds chance expectation in many other diseases.9 (Note that this review had less technical capability to detect organic diseases than is available today.)

Organic disease associated with schizophrenia is an extensive subject area that goes beyond psychiatry alone and involves the nature versus nurture debate. A consensual list of diseases associated with schizophrenia (secondary or aetiological psychosis) can be found in all psychiatry manuals.10 However, in clinical practice, these diseases frequently go unrecognised. The diagnosis of organic diseases associated with schizophrenia is an important issue in psychiatry, as well as an ethical one, especially if the diseases in question are treatable. This article provides a timely review of the psychiatric manifestations of NPC, as a recently licensed medication is now available to treat them.

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