Current Issues Neurometabolic Disease
Niemann-Pick Type C Disease – Report on Results from the Niemann-Pick Type C Patient and Healthcare Professional Survey
Hans H Klünemann,1 J Edmond Wraith2 and Frits A Wijburg3
1. Director, Memory Disorders Clinic, and Vice-director, Geriatic Psychiatry, Department of Psychiatry, University of Regensburg School of Medicine; 2. Professor of Paediatric Inherited Metabolic Medicine, Genetic Medicine, Central Manchester University Hospitals NHS Foundation Trust; 3. Professor of Clinical Metabolic Diseases and Paediatrician, Department of Paediatrics, Academic Medical Centre, University of Amsterdam
Abstract
Niemann-Pick type C disease (NPC) is a rare and progressive genetic condition that is associated with an abnormal accumulation of lysosomal lipids in the body, which manifests as a variety of neurological symptoms that range greatly in severity. Management focuses largely on treating symptoms, but recent developments have led to disease-specific therapy that can slow or stabilise the progression of neurological symptoms in some patients. The Niemann-Pick type C Patient and Healthcare Professional Survey conducted interviews with parents and carers of patients with NPC and with healthcare professionals to identify areas of NPC diagnosis, management and support that need improvement. Specifically, an emphasis was placed on increased awareness of the disease and disease symptoms with enhanced communication between doctors, their colleagues and parents of patients in order to facilitate the diagnostic process and the hope for earlier diagnoses, thereby enabling access to disease-specific treatment. The survey identified a need among families of patients with NPC for more support from doctors in the provision of information about the disease and about locally based social and psychological support, and for support from healthcare organisations that should coordinate all the available services. Such co-ordination could ensure that consistent support is provided for all aspects of patient care and for patients’ families and carers.
Keywords Niemann-Pick type C, diagnosis, management, support, outlook
Disclosure: Hans H Klünemann has received speakers fees from Actelion. J Edmond Wraith has received honoraria and travel grants from Actelion, has been principle investigator in Actelion-sponsored clinical trials and is a member of the NPC Registry Board. Frits A Wijburg has received grant support, honoraria for speaking engagements and consulting fees from Shire HGT and Genzyme Corporation. Acknowledgement: Editorial assistance was provided by Touch Briefings. Received: 22 October 2010 Accepted: 10 January 2011 Citation: European Neurological Review, 2011;6(1):12–5 Correspondence: Hans H Klünemann, Department of Psychiatry, University of Regensburg School of Medicine, Universitätsstr 84, 93053 Regensburg, Germany. E:
Hans.Kluenemann@medbo.de
Support: The publication of this article was funded by Actelion. The views and opinions expressed are those of the authors and not necessarily those of Actelion.
Niemann-Pick type C disease (NPC) is a pan ethnic, progressive neurological condition that is estimated to affect an estimated minimum of one in 120,000 Western Europeans.1
The neurological
symptoms stem from a characteristic autosomal recessive storage of various lysosomal lipids, including unesterified cholesterol, glycosphingolipids and sphingosine. These lipids accumulate in a number of organs in tissues, most noticeably in the liver, spleen and brain.2
which encodes the HE1 cholesterol binding protein has been identified. Rare cases of NPC have been reported to have this mutation that have a pattern of lysosomal storage that is virtually restricted to neurons rather than in bone marrow and viscera as well.5
NPC and its
genetic origins are therefore varied; it can be difficult to identify and its reported incidence may be an underestimate.6,7
Confirmation of NPC
However, the diagnosis of NPC is complicated by the clinical spectrum of the disease itself: the wide range of symptoms are not disease-specific, nor are they limited to specific stages of disease development. NPC has four subtypes arising from different mutations in the NPC1 gene, which codes for a membrane glycoprotein with multiple membrane-spanning domains that facilitates intracellular cholesterol trafficking and esterification. In addition, the NPC2 gene,
12
This excess storage of lipids, possibly by a number of mechanisms, causes progressive and disabling neurological symptoms such as clumsiness, ataxia, cognitive dysfunction and dysphagia, with increasing severity and decreasing quality of life in the later stages of disease.1,3,4
requires biochemical and genetic testing, histological analyses and imaging techniques. This often requires consultation with specialist centres, but the early symptoms must first be recognised by the initial physician for a referral to be made. Both the difficulties in diagnosis and the clinical symptoms can therefore impose a great emotional and economic burden on patients, their families and on society in general.
Management of Niemann-Pick Type C Disease There is no cure for NPC, and treatment has historically focussed on the alleviation of clinical symptoms to improve quality of life among patients. Management of neurological manifestations has been achieved using tricyclic antidepressants, central nervous system
© TOUCH BRIEFINGS 2011
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