Psychiatric disease in Niemann-Pick type C
Inborn errors of metabolism are serious diseases, which have been reported with an overall incidence of at least 40 cases per 100,000 (Applegarth et al., 2000). Several of these disorders may be undiagnosed in adulthood, and present with psychosis, as exemplified by Niemann-Pick type C, which is a very rare disease influencing approximately 1 case per 120,000 people. With such rare occurrence, it is not unexpected that the awareness, diagnosis and the potential implications of the disorders are poor, further impacting the onset of therapy.
An Actelion-sponsored educational satellite symposium “Difficult to diagnose psychoses: The case for organic causes of disease”, was held during the 24th ECNP Congress in Paris, France, September 2011. As reviewed in this issue of Key Opinions in Medicine, evidence for the possible brain psychopathology, improved diagnostics, and possible intervention, primarily in Niemann-Pick type C, was presented. Changes in both grey and white matter areas of the brain correlate with Niemann-Pick type C disease variables, which easy non-invasive tests may identify. Importantly, when initiated as soon as neurological or psychiatric symptoms become apparent, treatment with miglustat may help to slow progression of the Niemann-Pick type C, which also has been reported elsewhere (Patterson et al. 2007).
It is very encouraging that a significant effort is invested into research in the area, which together with improved awareness will help current and future patients suffering from these rare diseases. Gregers Wegener, Prof., Consultant, MD, PhD Centre for Psychiatric Research, Aarhus University, DENMARK
1. Applegarth DA, Toone JR, Lowry RB. Incidence of inborn errors of metabolism in British Columbia, 1969–1996. Pediatrics. 2000;105(1):e10.
2. Patterson MC, Vecchio D, Prady H, Abel L, Wraith JE. Miglustat for treatment of Niemann-Pick C disease: a randomised controlled study. Lancet Neurol. 2007;6(9):765–72.
A satellite symposium at the ECNP sponsored by Actelion Pharmaceuticals, Ltd. Paris, France, 04 September 2011
Increasing awareness of psychiatric illness in Niemann-Pick type C
More than 60 genetic disorders have been identified that may present with psychosis, including several inborn errors of metabolism (IEM). One such IEM, Niemann-Pick disease type C (NP-C), is a rare (~1:120,000 people), autosomal recessive disease that is invariably fatal. Although NP-C typically manifests with neurological symptoms in infancy, approximately one-third of cases have an adult onset and over the past few years, increasing numbers of patients have been diagnosed in adulthood. In >30% of adult patients, the first presenting features of the disease are psychiatric (Sévin et al. Brain. 2006;130:120–133), but delays in diagnosis can occur due to the heterogeneous and often subtle signs and symptoms. Treatment options for NP-C are limited. Treatment guidelines recommend initiation of therapy as soon as neurological or psychiatric signs appear. The role of psychoses in NP-C and other organic diseases was the focus of the Actelion-sponsored educational satellite symposium “Difficult to diagnose psychoses: The case for organic causes of disease”, held during the 24th ECNP Congress in Paris, France, September 2011. Delegates had the opportunity to liaise with colleagues and NP-C experts on the various aspects of psychiatric disease in NP-C. The satellite symposium was granted accreditation of two European CME credits by the European Accreditation Committee in CNS.
The Chair of the symposium, Dr Mark Walterfang of the Royal Melbourne Hospital, Australia, explained the session’s aim, to increase awareness of NP-C and other IEMs amongst patients with psychiatric disorders and highlight the key signs and symptoms that should trigger a search for IEMs. Dr Olivier Bonnot, of the Pitié-Salpêtrière Hospital, Paris, France, presented a diagnostic algorithm that has been developed to assist in diagnosing IEMs in patients with schizophrenia and Dr Hans-Hermann Klünemann, of the University of Regensburg, Germany gave some practical examples of some of the key diagnostic tests that can be used to identify metabolic psychoses that present with very specific, yet easily missable, signs. Dr Frédéric Sedel, of the Pitié-Salpêtrière Hospital, Paris, France, gave an overview of current treatment approaches in NP-C and finally, Dr Walterfang presented interesting findings on brain structural changes in NP-C.
- Psychiatric symptoms are often the first features of NP-C and other IEMs in adult-onset patients
- Straightforward, non-invasive tests, such as a focused eye examination, can identify specific features of organic disease (e.g. vertical supranuclear gaze palsy [VSGP])
- Treatment with miglustat can help to slow progression of NP-C, but therapy ideally needs to be initiated as soon as neurological or psychiatric symptoms become apparent
- Changes in both grey and white matter areas of the brain correlate with NP-C disease variables, and may be useful biomarkers of disease progression
A case study: Delayed diagnosis of NP-C
Dr Bonnot presented a case of a male who, on retrospective review, clearly exhibited signs and symptoms of NP-C from the age of 6 years, but was not diagnosed with NP-C until 21 years old. At 6 years of age, the patient had a tendency to fall frequently, displayed clumsy writing and fine movement, and had impaired drawing, writing, spelling and mathematics abilities. He was also hyperactive, impulsive and sometimes violent.
At 13 years of age, the patient had borderline intelligence associated with dysgraphia, attention deficit hyperactivity disorder, oppositional defiant disorder, and learning disorders, although he attended a normal school. The patient was hospitalised after being aggressive to his mother and subsequently attended a day hospital for 4 years. At this age, he had very few organic symptoms, including chronic diarrhoea and pes cavus, which required bilateral anterior tarsectomy.
At 18 years of age, a chance physical examination revealed bilateral extensor plantar response, distal muscular atrophy and distal hypoesthesia. However, it was not until he was 21 years old that elevated plasma cholesterol (cerebrotendinous xanthomatosis) was found and the boy was diagnosed with NP-C. With treatment and help for his learning disorders, the boy’s condition has improved since diagnosis. His sister was subsequently diagnosed with NP-C and is also receiving treatment.